Term
|
Definition
| What the body does to the drug. |
|
|
Term
|
Definition
| What the drug does to the body. |
|
|
Term
| What are the most commonly target receptors? |
|
Definition
| 40% of drugs target GPCRs. |
|
|
Term
|
Definition
| Absorption, Distribution, Metabolism, Excretion |
|
|
Term
| What are 4 ways a drug can be transported? |
|
Definition
Passive: Paracellular (between cells), Diffusion (through cells) - lipid diffusions is used by the vast majority of drugs.
Active: Facilitated diffusion, and Drug transporters |
|
|
Term
| Fenestrated vs Sinusoidal |
|
Definition
Fenestrated - Capillary endothelium
Sinusoidal - basement membrane |
|
|
Term
| What are the two types of aquaporins? |
|
Definition
| 1. Aquaporins 2. Aquaglyceroporins |
|
|
Term
| 4 types of active transport. |
|
Definition
| Primary active transporters, Secondary active transporters, Facilitated diffusion, transcytosis. |
|
|
Term
|
Definition
| ATP binding cassette transporters. Primary active transporters - use ATP to move something against its concentration gradient. Usually used for efflux. |
|
|
Term
|
Definition
| Solute carrier transporters. Secondary active transporters or facilitated diffusion. Couples uphill transport w/ downhill transport w/ a net downhill energy. |
|
|
Term
|
Definition
| Use of primary active transporters to pump drugs out of the cells. These transporters may be over expressed in tumors to make them chemo resistant. |
|
|
Term
|
Definition
| P-glycoprotin - a pump that helps to remove toxins from the body. A defense mechanism. Over expression in cancer cells makes them resistant to chemotherapy. |
|
|
Term
| Symporters vs Antiporters |
|
Definition
| Both secondary active transport. Symporters move the solutes in the same direction. Antiporters move them in opposite directions. |
|
|
Term
|
Definition
| Carrier mediated transport that doesn't require energy input. If this is coupled to the blood or metabolism of the molecule, the gradient will continuously favor more diffusion. |
|
|
Term
|
Definition
| Net transport in one direction. |
|
|
Term
|
Definition
| Tranport through the cell via vesicles. Endocytosed on one side, exocytosed on the other. Endocytosis can be receptor mediated, caveolae mediated (pits w/ cholesterol receptors), and adsorptive mediated (polycationic peptides bind w/- charges on cell membrane) |
|
|
Term
| Vesiculo-vaculo Organelles |
|
Definition
| Basically, transcytosis by a channel formed of connected endocytotic vesicles. |
|
|
Term
|
Definition
| Diffusion through "tight junctions". Claudin 5 - impermeable. Claudin 2 - permeable. These junctions are dynamically controlled by things like histamine and VEGF. Even the permeable ones only allow passage of very small particles. |
|
|
Term
| How can you take advantage of transport mechs? |
|
Definition
| Creating a drug w/ a similar structure to a natural compound. It can then piggyback on those transport mechs. |
|
|
Term
|
Definition
| Neutral forms penetrate membranes. You can create ion trapping effects due to different pHs across membranes. |
|
|
Term
| Henderson-Hasselbach Equation |
|
Definition
pH = pKa + log ([Unprotonated]/[Protonated]) or
pH = pKa + log ([A-]/[HA]) or
pH = pKa + log ([B]/[BH+]) |
|
|
Term
|
Definition
| The movement of a drug from the site of administration to the central compartment of systemic circulation. |
|
|
Term
| Intrathecal drug administration |
|
Definition
|
|
Term
|
Definition
| Administered by other means than the mouth or alimentary canal. (injection) |
|
|
Term
|
Definition
| Disintegration of the dosage form, dissolution of the active ingredients. |
|
|
Term
| Where are most oral drugs absorbed? |
|
Definition
| The small intestine - due to surface area and transit time. |
|
|
Term
| What are two factors affecting oral absorption? |
|
Definition
Direct interaction: drug may be destroyed by gastric pH or digestive enzymes, or physiological factors like gastric emptying time being slowed by foods (this leads to degradation - longer in low pH)
GI Effects: Drug metabolism in the gut, and transport. |
|
|
Term
|
Definition
| Drugs may be metabolized in the gut and then the liver before gaining access to the systemic circulation. |
|
|
Term
| What does grapefruit juice do? |
|
Definition
| It inhibits the OATP uptake transporters, and leads to a 60% decrease in CYP3A4 action in the gut (a metabolizer). |
|
|
Term
|
Definition
| The amount of the drug dose that actually makes it to the plasma and is available for action. |
|
|
Term
| What is an advantage of Rectal administration of a drug? |
|
Definition
| 50% of the venous drainage from the rectum bypasses the liver. Also can be given in instances of vomiting, and non-cooperation. However, rectal absorption is erratic. |
|
|
Term
| What is a benefits and risks of IV? |
|
Definition
| 100% bioavailability, immediate action (emergency). You can overdose the patient easily - once the drug is injected there's no going back. |
|
|
Term
| What mechanisms of absorption does intramuscular injection use? |
|
Definition
| Simple diffusion (lipid soluble), through loose macula occludens, via transcytosis - for macromolecules like hormones. |
|
|
Term
| Benefits of intrathecal injection |
|
Definition
| Bypasses the blood brain barrier and the blood CSF barrier. Can be used to treat brain infections w/ antibiotics. |
|
|
Term
| Topical Application drawbacks |
|
Definition
| Only highly lipid soluble drugs can be absorbed this way. |
|
|
Term
| Pharmaceutical equivalence vs. bioequivalence |
|
Definition
Pharmaceutical - same active ingredient, same dose, same form, same route of administration
Bioequivalence - Same bioavailability of the active ingredient.
These do not always come together. |
|
|
Term
|
Definition
| How the drug is delivered to the different tissues/areas of the body. |
|
|
Term
| Initial, second and final drug distribution phases |
|
Definition
| Initial - To areas with high blood flow: to brain, heart, liver, kidneys. Second - to muscle, most viscera, skin and fat. Final - Depends on the affinity of the drug for the tissue, lipid soluble go to all areas (adipose tissue), ionized stay in plasma and interstitial compartments (unless low MW or analog of a natural nutrient). |
|
|
Term
| Describe the Blood brain barrier - anatomically and biochemically. |
|
Definition
Anatomical - No pores, fenestrations, vesicles. Tight junctions. Limited extracellular space (astrocyte end foot processes)
Biochemical - ABC transporters (P-gp) are important for drug efflux. |
|
|
Term
| What can penetrate the BBB? |
|
Definition
|
|
Term
|
Definition
| Choroid plexus secretes CSF. Tight junction leads to the barrier. Not significant compared to the BBB. |
|
|
Term
| What is one way around the BBB? |
|
Definition
| Monoclonal antibody to insulin receptors. "Trojan horse" |
|
|
Term
| List some of the organs outside the BBB. |
|
Definition
| Sensing organs, neurosecretory organs (pituitary), Choroid plexus, |
|
|
Term
| How do plasma proteins affect distribution? |
|
Definition
| Drugs can bind to them, especially anions to albumin. This effectively inactivates the drug lowering the effective concentration of the free drug and requiring higher dosing. These proteins can also serve as storage depots for prolonged release. |
|
|
Term
| What are two concerns w/ plasma protein binding? |
|
Definition
| Some drug dosing must be adjusted in patients w/ hypoalbuminemia. Also, other drugs may displace the drug that was bound leading to higher free concentrations. It is important to monitor the drug free concentration, not just total plasma concentration. |
|
|
Term
| Volume of distribution - Vd |
|
Definition
| The apparent volume in which a drug appears to be homogenously dissolved. |
|
|
Term
| Elimination Clearance - CLe |
|
Definition
| That part of the volume of distribution from which all drug is irreversibly removed per unit time. |
|
|
Term
|
Definition
| 60% is water. 40% intracellular, 20% extracellular. - 16% interstitial, 7% blood volume - 4% plasma 3% RBCs (intracellular). Math works. |
|
|
Term
|
Definition
|
|
Term
|
Definition
| % of a drug removed for each unit run through the filter. |
|
|
Term
|
Definition
| % of a drug removed for each unit run through the filter. |
|
|
Term
|
Definition
| That volume (portion of Vd) per unit time from which all substance appears to be irreversibly removed. This measure doesn't change over time. |
|
|
Term
|
Definition
| Continuously changing, since the concentration of the drug keeps dropping as we remove it. |
|
|
Term
|
Definition
| Glomerular filtration rate (GFR) = Cle |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Time needed for the amount of drug in the body to decrease by 50%. |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| The window of concentrations between which the patient responds well, and there are limited adverse effects. |
|
|
Term
| What are the different phases in drug delivery? |
|
Definition
| Distribution, redistribution (to the other cylinders), and elimination. |
|
|
Term
| Why does it take longer to eliminate a drug if its been in the body longer at the same concentration? |
|
Definition
| It has equilibrated with the other tissues, so it must be removed from them, which takes more time. |
|
|
Term
| What is pharmacodynamic lag (hysteresis)? |
|
Definition
| The delay between drug administration and drug action. Usually due to the time it takes for the drug to diffuse into the location of action. |
|
|
Term
| How many half lives does it take to reach 90% of steady state? |
|
Definition
| 3.3 half lives. This is the point at which the drug is considered to be at it's maximal dose. |
|
|
Term
| Glomerular filtration: Why are more cationic molecules filtered than anionic? |
|
Definition
| The endothelium and epithelial podocytes are rich in negatively charged glycoproteins. |
|
|
Term
| What amount of the plasma is filtered by the glomerulus? |
|
Definition
|
|
Term
|
Definition
| Occurs at the proximal tubules. A major mech. for ionized (especially -) drugs. Some tightly bound drugs can use this pathway (since glomerular won't work for them). This can be blocked w/ certain drugs. |
|
|
Term
| Renal secretion uses what transporters? |
|
Definition
SLCs on the basolateral membrane: OATs and OCTs (Organic anion/cation transporters) for ionized drug uptake.
On the apical surface for export to the urine: ABC transporters P-gp & MRPs (for larger anions), the SLC NPT1 - Na dependent (for smaller anions) |
|
|
Term
| What is the OAT energy source in their secondary active transport of anions in tubular secretion? |
|
Definition
| Alpha- Ketoglutarate (a-KG) |
|
|
Term
| What mechanism do OCTs use to aid tubular secretion? |
|
Definition
|
|
Term
|
Definition
| Occurs in the distal tubule. Bi directional movement, but net reabsorption. Involves passive diffusion of non-ionized drugs (ion trapping effect). Altering urine pH can utilize this to sequester the ionized form in the urine and aid excretion. |
|
|
Term
| How does the retention time of water soluble vs lipid soluble drugs compare? |
|
Definition
| They have a shorter retention time due to the ion trapping effect. Lipid soluble have a much longer retention time due to reabsorption. |
|
|
Term
| What is the size for glomerular filtration? Bile excretion? |
|
Definition
| GF: 60-100nm Bile only important for things w/ a MW >300 |
|
|
Term
| What does metabolization in the liver do? |
|
Definition
| It creates more polar metabolites. These are then actively transported to the bile or back to the blood. Now they can be more easily excreted. |
|
|
Term
| What is the space of Disse? |
|
Definition
| The area around the hepatocytes (not the canaliculi). |
|
|
Term
|
Definition
| A flippase in the liver. Important for its role in adding phospholipids to the bile. A defect here promotes lithogenicity of the bile (crystallization of cholesterol). Can block bile flow. |
|
|
Term
|
Definition
| They export cholesterol and phytosterols into the bile. Defects in them can cause sitosterolemia (high plasma phytosterol levels). This can lead to xanthomas and premature atherosclerosis. |
|
|
Term
|
Definition
| A process wherein a drug is absorbed, metabolized in the liver (as a glucuronide), excreted as bile, and then cleaved by glucuronidases in the colon liberating the drug to be re-absorbed. |
|
|
Term
|
Definition
| When enzymes that are present for endogenous reactions also metabolize xenobiotics. |
|
|
Term
|
Definition
| "strangers" to "biological systems". Agents that are not natural to the body that enter via food, or as drugs. |
|
|
Term
| Why is metabolism important? |
|
Definition
| Because without it we couldn't get rid of lipophilic drugs. |
|
|
Term
| Phase I metabolism does what? |
|
Definition
| HORs (hydrolysis, oxidation, reduction) place an alluring functional group on the drug to make it more polar and provide a reactive center for phase II reactions. |
|
|
Term
| Phase II metabolism does what? |
|
Definition
| SAGGMeth (Sulfation, Acetylation, Glucuronidation, Glutathionine, Methyltion) Make the drug more polar by covalently conjugating the drug at the reactive center provided by Phase I. |
|
|
Term
| What is the most common phase I reaction? |
|
Definition
| Oxidation via CYPs (86% of useful drugs use this). CYP3A4 is the most common of the CYPs |
|
|
Term
| What is the most common Phase II reaction? |
|
Definition
|
|
Term
|
Definition
| Benzodiazepine. A sedative. This drug is a prototypical example of the Phase I, II metabolism (CYP3A4 hydroxylation, followed by glucuronidation) making it very water soluble and ready for excretion. |
|
|
Term
|
Definition
| Occurs via ester hydrolysis or epoxide hydrolysis (protect from cancer causing epoxides). |
|
|
Term
|
Definition
| Performed largely by CYPs. Include Hydroxylations, and oxidative dealkylations. Require a reductase (feeds 2 electrons) and the oxydase. |
|
|
Term
|
Definition
| The liver (ER of hepatocytes) and the intestines. |
|
|
Term
| What is important about Cimetidine? |
|
Definition
| It is a competitive H2 histamine receptors. It also inhibits a lot of CYPs. |
|
|
Term
|
Definition
| Valium. Is metabolized by CYPs in two steps: N-dealkylation followed by hydroxylation. Both metabolites are active, making the drug very long acting. Then it is glucuronidated. |
|
|
Term
|
Definition
| Addition of an electron or hydrogen atom. |
|
|
Term
|
Definition
| Phase II reaction, binds a sulfate group to a drug to make it polar and excretable. Example is Acetaminophen where SO3H is bound at the Hydroxyl site. |
|
|
Term
|
Definition
| Occurs via N-acetyltransferases (cytosolic enzymes requiring Acetyl CoA). This reaction is unusual since it makes drugs less polar. |
|
|
Term
|
Definition
| Occurs via glucuronyl transferases. The most common phase II reaction. Enzymes in the smooth ER and requires UDP glucuronic acid (this is added to the enzyme through an activation process. Acetominophen is an example of this as an alternative to sulfation. |
|
|
Term
| What type of metabolism changes w/ age? What doesn't? |
|
Definition
| CYPs decrease w/ age. Glucuronidaton doesn't. |
|
|
Term
|
Definition
| Is transfered to toxic electrophiles via glutathione-S transferase (GST). One of the most common liver enzymes. Also linked to resistance to chemo. |
|
|
Term
|
Definition
| Occurs via methyltransferases. S-adenosylmethionine is the donor. Adds a methyl group often to N, S, or O sites on aromatic rings. |
|
|
Term
| Acetaminophen: the whole story |
|
Definition
| At low doses undergoes phase II metabolism via Glucuronidation and sulfation. However, at high doses CYPs begin to metabolize it and this produces toxic intermediates. These intermediates can be metabolized via glutathion conjugation, but if not enough GSH is present liver cell death results. GSH can't be used as an antidote since it doesn't cross membranes well. N-acetylcysteine. It acts in the same way as GSH. |
|
|
Term
| Why does succinylcholine matter? |
|
Definition
| Polymorphisms (pseudocholinesterase) makes you unable to metabolize it and temporary paralysis may result. |
|
|
Term
|
Definition
| This is the most important polymorphism in drug metabolism. Trimodal distribution (ultrametabolizers and poor metabolizers). Usually high metabolism = higher dose. Opposite true w/ codeine (a prodrug) - this shouldn't be used on poor metabolizers. |
|
|
Term
|
Definition
| These have some polymorphisms as well. Particularly CYP2C19 - slow metabolizers exist (Asians). |
|
|
Term
|
Definition
| Exhibits important polymorphisms. Slow metabolizers exist. In DiaZEPAM metabolism this already long acting drug can have a half life over 4x longer than normal. Also OmePRAZOLE (proton pump inhibitor) degradation. Dosage may need to be adjusted. |
|
|
Term
|
Definition
| N-acetyltransferases (NAT) - fast and slow exist. Slow can lead to toxic effects (Isoniazid). |
|
|
Term
| Glutathione Polymorphisms |
|
Definition
| GST and GST null phenotypes exist. Body loses some of its protective function, risk of cancer increases. |
|
|
Term
| Why is CYP3A4 so commonly used? |
|
Definition
| It's large binding domain allows for promiscuity. |
|
|
Term
|
Definition
| Important in that it causes Acetaminophen toxicity. It is induced by ethanol. Ethanol also reduces GSH leading to less recovery of the toxic product and greater toxicity. |
|
|
Term
| Factors affecting the CYPs |
|
Definition
| CYP1A causes the toxicity of pollutants. Grapefruit juice inhibits CYP3A4 and CYP2E1. St. John's Wart induces both. Ginko induces CYP2C19 (omePRAZOLE). Echinacea induces CYP3A4 and inhibits CYP1A2. Drugs can be substrates and inhibitors of CYPs (competitive inhibition). |
|
|
Term
|
Definition
| A packaged set of genes, capable of invading the cell and using the cell machinery to replicate. Inert without the cell. Measure 10nm to several hundred nm. |
|
|
Term
| Consequence of viral invasion |
|
Definition
| Illness due to infection (extensive cell death). Illness due to persistent infection (chronic tissue damage. Cancer. |
|
|
Term
| How are viruses classified? |
|
Definition
| Physical structure - helical (rods) or icosahedral (spherical) and type of code inside (DNA/RNA etc.) |
|
|
Term
| Capsomer - the protein that coats a virus. |
|
Definition
| Can be the outer layer of a virus, or can be inside an outer membrane. |
|
|
Term
| Why may cells be resistant to a virus? |
|
Definition
| They lack the receptors for viral entry. Viruses are specifically targeted to certain receptors. |
|
|
Term
|
Definition
| Viral infection that is actively generating more virions. Usually associated w/ cell death. 1. Attach 2. Penetrate 3. Disassemble - release genome 4. Express viral genes 5. Replicate genome 6. Assemble virions 7. Release from cell. |
|
|
Term
| Adenovirus and Herpes virus are examples of what? |
|
Definition
| Double stranded DNA w/ early and late transcription. Early proteins replicate the genome, late are structural. |
|
|
Term
|
Definition
| Polio. +ssRNA. Produces one large polyprotein that is later broken up. |
|
|
Term
| Orthomyxoviruses (influenza) |
|
Definition
| -ssRNA. Virus must carry its own polymerase since the cell doesn't have the machinery for this. |
|
|
Term
|
Definition
| ssRNA carrying reverse transcriptase. Converted to DNA once in the cell. DNA then runs the show. |
|
|
Term
|
Definition
| Can happen either by killing the cell and lysing the membrane, or using cellular mechanisms to get out without killing the cell. |
|
|
Term
| What happens to a virally infected cell? |
|
Definition
| Usually death either from cytotoxic viral products or host responses. Most retroviruses (not HIV) and Hepadnaviruses are compatible with cell survival. |
|
|
Term
|
Definition
| The virus has a dormant phase. You can't eradicate these viruses. Viral genome only replicates w/ cell division. Few if any viral proteins expressed. If expressed may be non-immunogenic. This acts as a reservoir for reactivation of infectious virus. Herpes virus (coldsores). |
|
|
Term
|
Definition
| The microbes that make up our normal flora |
|
|
Term
| How are prokaryotes different from eukaryotes (4 ways)? |
|
Definition
| Cell wall, no nucleus, no classical organelles, no introns |
|
|
Term
| What are the 4 types of bacterial morphology? |
|
Definition
| Cocci - spheres, Rods (bacilli), Coccobacilli rod-spheres, Spirochetes - spirals |
|
|
Term
| What is the general size of bacteria? |
|
Definition
|
|
Term
|
Definition
| Consists of cell wall and cytoplasmic membrane |
|
|
Term
| Cytoplasmic membrane (bacteria) |
|
Definition
| Aka plasma membrane. Inner lipid bilayer (only bilayer in gram positive). Touching cytoplasm. Synthesizes cell wall components. |
|
|
Term
|
Definition
| Gives its shape. Rigid. Protect against lysis due to osmotic pressure. |
|
|
Term
|
Definition
| Aka murein. An important part of the bacterial cell wall. Thick in gram positive. Antibiotic target. |
|
|
Term
|
Definition
| Made of N-acetylglucosamine and N-acetylmuramic acid. Peptide of alternating L and D AAs. 3rd AA of some peptides is crosslinked to terminal AAs of other peptides. Crosslinking is guided by Penicillin Binding Protein (PBP). |
|
|
Term
|
Definition
| Penicillin and its family of antibiotics. Attack the PBPs. |
|
|
Term
|
Definition
| Binds to the terminal AA in the Peptidoglycan side chains to prevent cross linking. |
|
|
Term
|
Definition
| A naturally occurring antibiotic found in saliva, tears, and mucous secretions. Cleaves specific bonds in peptidoglycan yielding NAGA and NAMA disaccharides. |
|
|
Term
| Gram positive vs. Gram negative |
|
Definition
+: Thick peptidoglycan wall
-: Wall of thin peptidoglycan and outer membrane. |
|
|
Term
|
Definition
Crystal violet - iodine - alcohol - safranin.
Purple - gram positive. Pink - gram negative. |
|
|
Term
| Bacteria that aren't visualized with Gram Staining. |
|
Definition
Mycobacteria: Have long-chain fatty acids. Acid-fast staining must be used.
Spirochetes: Poorly visualized due to thinness. Must use dark-field microscopy.
Mycoplasma, Chlamydia: No cell wall.
Rickettsias, Legionella: Must use tagged antibodies to visualize legionella. |
|
|
Term
|
Definition
| Long polymers of either glycerol phosphate or ribitol phosphate that also contain sugars and amino acids. Attached to the cell wall or cytoplasmic membrane (lipoteichoic acids). May function as adhesins. |
|
|
Term
|
Definition
| Has a thin peptidoglycan layer along with an outer membrane to make up the wall. Outer membrane contains porins. Phospholipis on outer leaflet are replaced by lipopolysaccharide (LPS). |
|
|
Term
| Periplasm/Periplasmic space |
|
Definition
| The space between membrane in gram negative bacteria. Contains the peptidoglycan layer. |
|
|
Term
|
Definition
| Outer part of outer membrane. Forms a good permeability barrier. Composed of Lipid A, Core polysaccharide (7-9 sugar residues), O Antigen (repeating units of 3-5 sugar residues. Up to 40 units long). |
|
|
Term
|
Definition
| Resists complement deposition, and therefore inhibits complement mediated killing (serum resistant). However, with repeated exposure it is recognized by specific antibodies which mediate bacterial clearance. Also allows for serotyping. |
|
|
Term
|
Definition
Due to lipopolysaccharide activity (Protein A responsible). Low concentrations: Triggers immune response (fever, stimulates B cells & macrophages, activates complement, etc)
High concentrations: Causes septic shock |
|
|
Term
|
Definition
| LPS binds to LPS binding protein. This interacts with CD14 receptors on monocytes and macrophages. These interact w/ TLR-4 and lead to pro-inflammatory cytokine (IL-1, TNF) production - leading to the toxicity. |
|
|
Term
|
Definition
| Layers of organic polymers attached to the exterior of bacteria. Usually polysaccharides (not antrax - poly-D-glutamic acid). 95% water - prevent desiccation. Also prevent phagocytosis by preventing complement activation. |
|
|
Term
| What 3 bacteria have capsules as an important part of their virulence? |
|
Definition
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus influenzae
Can causes septic shock in asplenic patients. |
|
|
Term
|
Definition
| A polymer of flagellin monomers. Hollow filament, flagellin passes through and self assembles at tip. Flexible hook attaches to basal body in the bacterial envelope. The basal body acts as a motor for the flagella. |
|
|
Term
|
Definition
| Flagella can move at 40-60 rps. Energy from flow of protons into the cell. Counterclockwise = running, clockwise = tumbling. Can move as fast as 100 cell lengths/sec. |
|
|
Term
|
Definition
| The ability of bacteria to move toward attractants and away from repellants. Chemoattractant delays switch from running to tumbling, leading to net movement. |
|
|
Term
|
Definition
| H antigens (flagella), O antigens (O side chains), K antigens (capsules). |
|
|
Term
|
Definition
| TLRs are sentinels in the immune system that recognize relatively conserved bacterial antigens. |
|
|
Term
|
Definition
| Aka Fimbriae. Long filimentous structures on the surface of bacteria made primarily of pilin. They mediate adherence to host cell receptors (provide binding specificity), twitching motility (by extending and contracting back into the bacteria), and biofilm formation. |
|
|
Term
|
Definition
| Site where bacterial genome replication starts. Can start again before first one finishes. Allows for rapid replication. DNA gyrases allow for chromosomal separation upon cell division. |
|
|
Term
|
Definition
| Where one promoter is linked to multiple genes. |
|
|
Term
|
Definition
| 70S - has 30S and 50S subunits. Different from Eukaryotes (80S - 60/40) |
|
|
Term
| Why is PCR useful for bacteria? |
|
Definition
| We can use it to identify non-culturable bacteria. Amplify the 16S rna part of the 30S ribosomal subunit. Eg: Whipple's Disease |
|
|
Term
|
Definition
| Aka Endospores. Metabolically inactive forms of bacteria. Highly resistant. Few can make them (anthrax). Develop within vegetative cells. |
|
|
Term
| Iron as a bacterial nutrient. |
|
Definition
| Iron is important. Body knows this and keeps serum iron low. Bacteria use siderophores to remove iron from host molecules and then the bacteria can take it up. |
|
|
Term
| Bacterial Metabolism Options |
|
Definition
Fermentation (O2 independent) - Substrate level phosphorylation generates energy. Low energy production. End product acids or alcohols.
Respiration (O2 dependent) - electron transport chain. High energy production. |
|
|
Term
|
Definition
| Pumping protons outside the membrane and then harvesting the energy as the re-enter to make ATP. |
|
|
Term
|
Definition
| Means the bacteria contains cytochrome c - and therefore has electron transport chain machinery - aerobic. Metabolism in general can be used as an identification tool. |
|
|
Term
| Phase variation vs Antigenic variation (bacteria) |
|
Definition
Phase Variation: Turning on or off production of particular surface proteins such as flagellin or pili.
Antigenic variation: The ability to continue to make a surface protein but change its antigenic form. Done by swapping genes coding for pili with different antigens into the active locus in Neisseria gonorrhoeae. |
|
|
Term
| Why is oxygen toxic to many bacteria? |
|
Definition
| Oxygen itself is only mildly toxic. The real toxicity is because oxygen gives rise to hydrogen peroxide (H2O2) and a superoxide anion (O2-) which are very reactive and toxic. |
|
|
Term
| How do bacteria protect against oxygen toxicity? |
|
Definition
| Superoxide dismutase (takes care of the superoxide anion making O2 and Hydrogen peroxide), and catalase (takes care of hydrogen peroxide making 2 water and O2). |
|
|
Term
| What are the 4 main types of bacteria (based on metabolism with or without oxygen)? |
|
Definition
Aerobe - require oxygen.
Anaerobe - dies in the presence of oxygen.
Facultative - respires w/ oxygen, ferments w/out oxygen.
Indifferent (aerotolerant anaerobe) - ferments w/ or w/out oxygen. |
|
|
Term
|
Definition
| Bacteria that grow best in an environment with less oxygen than is normally found in the air. Eg: Strep throat. |
|
|
Term
| What are the different types of media used to culture bacteria? |
|
Definition
Enrichment media: Encourages the growth of certain organisms.
Selective media: Contains one or more components that inhibit the growth of certain groups of organisms.
Differential media: Allows colonies of certain organisms to be distinguished from colonies of other organisms. |
|
|
Term
| Obligate intracellular bacteria |
|
Definition
| Bacteria we just can't grow on plates. Rickettsia, Chlamydia. Must be grown on monolayers of tissue. |
|
|
Term
|
Definition
| 3D communities of bacteria and ECM that grow on solid surfaces. Often form at solid-air, or solid-liquid boundaries. Can form on prosthetic material in the body. Resistant to antibiotics. |
|
|
Term
| Bactericidal vs bacteriostatic activity |
|
Definition
| Antibiotics may be either. Bactericidal - kills the bacteria. Bacteriostatic - prevents growth and division, relies on the immune system to finish it off. |
|
|
Term
| MIC (minimum inhibitory concentration) vs MBC (minimum bactericidal concentration) |
|
Definition
| In reality you'll only use MIC. The least amount of antibiotic needed to prevent growth under standardized conditions. MBC is the least amount required to kill a given amount (usually 99.9%) in a given time. Not used because it's too hard to measure. |
|
|
Term
| What are the susceptibility tests? (bacteria) |
|
Definition
| 1. Dilution tests: measure MIC by adding bacteria to different dilutions of antibiotics 2. Kirby-Bauer test - use disks w/ different amounts of antibiotic. Measure zones of growth inhibition. 3. E-test - Use a strip w/ antibiotic gradient. MIC is where zone of inhibition meets the strip. |
|
|
Term
|
Definition
| DNA released by some cells is taken up by others. Only certain bacteria naturally competent (Streptococcus pneumoniae, Bacillus spp., Haemophilus influenzae, Neisseria spp.). E. coli is artificially competent (important for "cloning") |
|
|
Term
|
Definition
| Bacteriophages (viruses for bacteria) act as vectors to introduce DNA from donor bacteria to recipient bacteria via infection. General: DNA randomly incorporated into the capsule. Specialized: DNA from host is transferred w/phage DNA. - of more limited importance. |
|
|
Term
|
Definition
| Bacterial "sex". Unidirectional transfer of genetic material between bacteria. Mediated by “conjugative plasmids” and “integrative and conjugative elements (ICEs). |
|
|
Term
|
Definition
| Conjugation. Encodes the conjugation machinery (sex pilus). A copy of the plasmid is then passed to the recipient. Can rarely integrate into the genome in which case that part of the genome and part of the donor cell chromosome can be passed. |
|
|
Term
| Types of bacterial genetic elements (4) |
|
Definition
| 1. Transposable elements 2. Plasmids 3. Bacteriophages 4. Integrons. |
|
|
Term
|
Definition
| DNA fragments that mediate their own movement from one location on a chromosome or plasmid to another. Important in the transfer of antibiotic resistance, and in the creation of mutations. Can be insertion sequences or transposons. |
|
|
Term
|
Definition
| Smallest transposable elements. Encode transposases - these recognize inverted repeats cuts and reseals DNA allowing movement from one location to another.. |
|
|
Term
|
Definition
| Carry transposition genes plus other genes. May encode antibiotic resistance or virulence determinants. Transferred from bacteria to bacteria by transferrable genetic elements Eg: via phages and plasmids. |
|
|
Term
|
Definition
| Plasmids that are capable of transferring themselves to other bacteria. Eg: F plasmid, R plasmid - carry antibiotic resistance (often multiple resistance). |
|
|
Term
| What are the two types of bacteriophages? |
|
Definition
Virulent phages - kill the bacteria. Lytic infection.
Temperate phages - Lysogenic infection. May integrate into the bacterial chromosome and be quiescent for some time. |
|
|
Term
|
Definition
| Phages acquire genes that change the characteristics of the bacterium. These genes are unrelated to phage processes. Conversion occurs when a host bacterium acquires new properties due to these, some of which may be important in virulence. |
|
|
Term
|
Definition
| Genetic entities that capture exogenous gene cassettes and ensure their expression. Not mobile but linked to mobile elements. Has 3 parts: Promoter, Primary recombination site downstream from the promoter, and a gene encoding integrase which inserts gene cassettes into the integron. Most cassettes are a single gene for antibiotic resistance. If it has multiple cassettes it works as an operon. |
|
|
Term
|
Definition
| Can either refer to 1 a bacteria's ability to grow with or without oxygen or 2 a bacteria's ability to grow both inside and outside eukaryotic cells. |
|
|
Term
| Bacterial growth cycle (3 phases) |
|
Definition
| 1. Lag phase (hrs 0-5) 2. Exponential phase (hrs 5-10) - bacteria can divide as fast as every 20 min or as long as every 12-24 hrs. 3. Stationary phase (hrs 10+) |
|
|
Term
| What cells are lost in an HIV infection? |
|
Definition
| CD4+ T cells and macrophages. This leads to primary acute mononucleosis-like syndrome early (in some cases), and susceptibility to opportunistic infections later. |
|
|
Term
| Why does HIV exhibit a high degree of antigenic (and genetic) variability? |
|
Definition
| An error prone reverse transcriptase. |
|
|
Term
| Describe the structure of an HIV virion? |
|
Definition
| A membrane coat w/ structural proteins on the surface targeting it to CD4+ cells, as well as part of the envelope. Inside the envelope is a triangular capsid containing two copies of the +ssRNA genome and the 2 enzymes needed for the viral life cycle (reverse transcriptase, and integrase). |
|
|
Term
| Why is HIV different from most animal retroviruses? |
|
Definition
| It kills its host cell. This is critical in the pathogenesis of the disease. |
|
|
Term
| What do gag, pol and env encode for in HIV? |
|
Definition
| gag encodes a large protein that is chopped up to make the core. pol encodes the proteases to chop gag as well as reverse transcriptase and integrase, env encodes the structural components of the virus (envelope). |
|
|
Term
|
Definition
| A viral precursor. A host cell that has the viral genes incorporated into its genome. |
|
|
Term
| What are the 6 HIV accessory factors and their purpose? |
|
Definition
| 1. Vpr - Imports the pre-integration complex into the nucleus. 2. Vpu - Ubiquitinates CD4 in the ER causing its destruction 3. Nef - Removes CD4 and MHC class 1 from the cell surface (helps avoid immune detection for a time) 4. Tat - enhances viral gene expression 5. Vif - overcomes an innate cell defense that would block production of infectious virions. 6. Rev - Binds the rev response element and directs export of unspliced messages to the cytoplasm. |
|
|
Term
| HIV has a "latent" stage. Describe this. |
|
Definition
| HIV expresses clinical latency, but not true latency. The virus is actively dividing (although at any given time, there are some latent cells). The host's T-cell numbers just haven't dropped yet to show symptoms. This stage can last years. |
|
|
Term
| Why can't the immune system defeat HIV? |
|
Definition
| 1. It escapes neutralizing antibodies by antigenic variation and latency in some cells. 2. Cytotoxic T cells actually exacerbate the problem by eliminating CD4+ cells. 3. The loss of CD4+ cells decreases the protective response. |
|
|
Term
| Does HIV resistance exist? |
|
Definition
| Yes. They don't have a functional CCR5 gene, must be important at the point of entry for HIV. |
|
|
Term
| What is the treatment for HIV and how does it work? |
|
Definition
| HAART (highly affective anti-retroviral therapy): often two nucleoside analogs plus one protease inhibitor. Reverse transcriptase inhibitors can also be used. |
|
|
Term
|
Definition
| A disease communicable to humans from other animals. Eg: HIV |
|
|
Term
|
Definition
| ARthropod-BOrne (transferred by mosquitos or tics) and related viruses. +ssRNA viruses w/ membrane coats. Eg: West nile, hauntavirus, equine viruses |
|
|
Term
| What is the most common arbovirus? |
|
Definition
| Japanese Encephalitis Virus. More cases than all other arboviruses combined. Affect those w/ compromised immune systems. |
|
|
Term
|
Definition
| A coronavirus transmitted through droplets and feces. (10-20% of infected individuals require intensive care - Death rate of 6%). |
|
|
Term
| Polio is an example of what type of virus? |
|
Definition
| It is one of the enteroviruses. |
|
|
Term
|
Definition
| Grow a virus in a culture where it can only spread to adjacent cells. You then see how many plaques appear and use that to determine the titer. |
|
|
Term
| What two things are required for a vaccine to be viable? |
|
Definition
| 1. There can't be many serotypes of the disease you're targeting. 2. The virus has to cause a good natural immune response. |
|
|
Term
| How do picornaviruses (like polio) work? |
|
Definition
| They inject their +ssRNA into the cell. Acts as mRNA. Ribosomes pull it into the cell. Make one autocatalytic polyprotein. This then splits into the various component parts. |
|
|
Term
| What is the virus cytopathic effect (CPE)? |
|
Definition
| A virally infected cell will become very vesiculated (looks like it's boiling). It is producing viral proteins and preparing to release them from the cell. |
|
|
Term
| What are the 3 major gene components of picornaviruses and what do they do? |
|
Definition
| P1 - structural proteins, P2 - replication of the viral genome, P3 - has to do with the virus taking over the cell. |
|
|
Term
| Why is protein kinase R important? |
|
Definition
| It is a cellular mechanism to stop translation. Poliovirus inhibits this. |
|
|
Term
| How does poliovirus interact with the normal cellular machinery? |
|
Definition
| Polio stops translation by inhibiting the normal cap recognition machinery, and using a uncapped mechanism to focus the cell on translating only it's mRNA. This also prevents the production of interferon. It then wreaks havoc with the nucleus to prevent transcription. |
|
|
Term
| What are the 3 major viral causes of diarrhea? |
|
Definition
| Rotavirus, Norovirus, and Astrovirus. |
|
|
Term
|
Definition
| Fecal-oral transmission. dsRNA (rare - PKR senses that). Tripple layered capsule (makes very stable). Infects epithelial vili in small intestine. Secretes an enterotoxin leading to diarrhea. |
|
|
Term
|
Definition
| Part of the cytoplasm that is taken over and converted to a virus factory. |
|
|
Term
| Why doesn't PKR trigger with a rotavirus infection? |
|
Definition
| Has a structural polymerase inside to translate to mRNA. dsRNA never leaves the capsule, thus protecting from PKR recognition. |
|
|
Term
|
Definition
| Viral toxin causing diarrhea. Induces anion secretion via a transduction pathway. This leads to water release. |
|
|
Term
| What are 4 viruses that lead to the common cold? |
|
Definition
| Rhinovirus, Adenovirus, Coronavirus, Respiratory syncytial virus (RSV). |
|
|
Term
| Why do you keep getting colds? |
|
Definition
| 1. You never get the same cold - over 100 rhinoviruses 2. RSV is fusogenic and doesn't lead to a durable immune response. |
|
|
Term
| What diseases does parainfluenza typically cause? |
|
Definition
| Croup, bronchiolitis, pneumonia. Typically in children - you develop immunity. Only 4 serotypes. |
|
|
Term
|
Definition
| It is a respiratory virus causing fifth disease (erythema infectiosum; “slapped cheek”). Most common cause of infectious miscarriage. |
|
|
Term
| What is human bocavirus 1 (HBoV1) |
|
Definition
| A virus that causes acute respiratory tract infection (ARTI). Affects children. Always appears w/ other infections. |
|
|
Term
| How are measles, mumps, and rubella passed? |
|
Definition
| They aren't (vaccines). But if they are it is respiratory. |
|
|
Term
| Varicella zoster, and smallpox cause skin lesions. How are they acquired? |
|
Definition
| Respiratory. In through the nose/mouth, out through the skin. |
|
|
Term
| Name two herpes viruses that are transmitted via the respiratory system. |
|
Definition
| EBV and Varicella zoster. |
|
|
Term
| Antigenic shift vs. antigenic drift |
|
Definition
Drift: spontaneous mutations in antigens (HA & NA for the flu).
Shift: two viruses w/ different antigens infect the same person and reassort genes expressing some antigens from both.
Both of these help the virus avoid a previously established immune response. |
|
|
Term
|
Definition
| Orthomyxo virus. Structurally an enveloped helix. -ssRNA (segmented). Has N (NA) & H (HA) - glycosylated membrane bound proteins on the surface. It also has a structural RNA dependent RNA polymerase (RdRp) which functions as a transcriptase and a replicase. Comes in 3 types (ABC). A is most important. |
|
|
Term
| How is influenza virus activated? |
|
Definition
| The cellular receptor for HA is sialic acid, which is everywhere. However, HA (the fusion protein) must be proteolytically cleaved by tryptase clara which is in the respiratory tract only determining tropism. HA becomes a loaded spring that is activated by low pH. In low pH it pops and fuses the membranes. |
|
|
Term
| Why is NS1 important for influenza? |
|
Definition
| It antagonizes interferon response. Non-structural protein. |
|
|
Term
|
Definition
| Done by Influenza. It steals the cap primers and pol II from cellular mRNA and uses it for its own mRNA. Allows it to express viral protein, and has the added benefit of inhibiting cell protein expression. Why viral mRNA synthesis and genome replication must occur in the nucleus. |
|
|
Term
|
Definition
| Anti-viral drugs (M2 channel blockers). Good against the flu. Blocks the acidification of the interior of the virus. Virus never activates. |
|
|
Term
| Why do pigs matter in the flu? |
|
Definition
| Birds are the major carriers of the flu. They express 2,3 sialic acid linkages. Humans express 2,6 linkages. Pigs express both, and therefore provide a perfect mixing ground where new strains that affect humans can develop. |
|
|
Term
| Hemaglutinin (HA) and Neuroaminidase (NA) |
|
Definition
HA: An envelope protein in influenza that mediates binding and entry into host cells. Also important for nomenclature. 17 subtypes have been identified.
NA: The other important antigen in influenza. 10 subtypes have been identified. |
|
|
Term
|
Definition
| When a virus gets to the blood. How the liver gets infected. |
|
|
Term
| HepA (HAV) - "infectious hepatitis" |
|
Definition
| A picornavirus like polio, an enteric virus that can spread. Naked +ssRNA. One serotype (vaccine available). No CPE. Liver damage due to immune response. Grows in hepatic cells (and) Kupffer cells and is excreted through the bile duct. Most likely to get it through travel - worse as an adult. |
|
|
Term
|
Definition
| Macrophage-like cell in the liver. |
|
|
Term
| HepB (HBV) - "Serum Hepatitis" |
|
Definition
| Hapadna virus - dsDNA. (Blood borne (like HIV). Envelope. No CPE. Liver damage due to immune response. Hard to grow in culture (like A). Can establish life-long chronic infections (especially in kids). Adults can handle better. |
|
|
Term
| How does a DNA virus usually work? |
|
Definition
| It uses cellular machinery (Pol II) to make mRNA and viral products, and uses a viral polymerase for replication of the DNA genome. |
|
|
Term
| How does a Hepadnavirus use cellular machinery? |
|
Definition
| HBV. Uses cellular machinery (Pol II, ribosomes) to make mRNA and viral proteins. Has a structural reverse transcriptase for replication to convert RNA into a DNA copy. |
|
|
Term
| How does the poly A tail work in HBV? |
|
Definition
| All of the genes start at different places and end in the same place so the poly A sequence only occurs once in the genome. Efficiency! |
|
|
Term
| What are sub viral particles (SVPs) and what is their role in HBV infection? |
|
Definition
| They are non-viral capsules. They are not infectious. Their role is most likely to act as decoys for the actual virus protecting it from the immune response. They carry the surface antigen (HBsAg) |
|
|
Term
|
Definition
| Hepatits B - e antigen. It is excreted during production of the virus. No one knows its purpose. It is not needed for replication or spread. It is however a good indicator of the highly infectious state, and therefore is a good clinical tool. |
|
|
Term
| Chronic HBV or HCV infection can lead to what? |
|
Definition
| HBV is the leading cause of cirrhosis worldwide. They can also lead to hepatocellular carcinoma and liver failure. |
|
|
Term
|
Definition
| HDV infection can only occur in someone who is also infected with HBV making it a dependovirus. -ssRNA. Must be housed in HBV coat (SVP). Kills hepatocytes by CPE (unlike HAV and HBV which only damage the liver through the immune response). Simultaneous transmission a problem, but bigger issue is if a chronic HBV gets HDV = superinfection. |
|
|
Term
|
Definition
| A special pathogen unique to the plant kingdom. HDV is viroid-like. |
|
|
Term
|
Definition
| Allows for HDV replication. Binds to pol 2 and contorts it to make it use RNA even though it’s DNA dependent. Because of this it doesn't need a structural polymerase. Delta antigen also gets the genome into the coat. |
|
|
Term
| Describe the genome of HDV |
|
Definition
| It is -ssRNA that self base pairs. It is autocatalytic (cleaves itself to begin replication). Only one open reading frame (ORF) and two forms of the delta antigen (large and small). |
|
|
Term
|
Definition
| Hard to find. A flavivirus, +ssRNA enveloped. Has a very high carrier state of 85% (as compared w/ 10% for HBV). Blood borne pathogen - was a contaminator of the blood supply. |
|
|
Term
|
Definition
| Unique family hepevirus. +ssRNA non-enveloped. The only zoonotic hepatitis virus. Is a fecal-oral virus (doesn't affect developed nations). Similar to HAV in consequences etc. but not structure. |
|
|
Term
| There are 3 alpha human herpes viruses (HHV). Can you identify their associated diseases? |
|
Definition
| Alpha (neuroinvasive - rapidly replicating) HHV1-3. 1. Cold sores 2. Genetial herpes (these two are the simplex viruses) 3. Varicela zoster |
|
|
Term
| Herpes sporadic encephalitis (HSE) |
|
Definition
| Rare manifestation of Herpes simplex virus. Goes to the brain. Stroke-like symptoms. Acyclovir is the best treatment, but must start early. |
|
|
Term
|
Definition
| Herpes Simplex keratitis - disease of the cornea. #1 cause of infectious blindness in the USA. Damage is due to the immune response. |
|
|
Term
|
Definition
| Sensory ganglion for the head. Where HSV lives and goes latent. Sacral ganglion for HSV2. |
|
|
Term
| Primary vs. Secondary host |
|
Definition
| Primary - naturally infected species. Typically experiences recurring benign symptoms due to successful latency. Secondary - dead end host. Infection leads to fatal encephalitis. Humans are a secondary host for herpes B, and monkeys are a secondary host for HSV. |
|
|
Term
| Describe the structure of Herpes virus |
|
Definition
| linear dsDNA, icosahedral capsule, tegument, membrane. It is replicated in the nucleus and has a complex non-lytic secretory pathway. |
|
|
Term
| How does the herpes capsid get into the nerve nucleus? |
|
Definition
| It utilizes dynein to transport the capsid to the nucleus. Then it uses kinesin to sent the fully assembled virus back down to the site of release. |
|
|
Term
|
Definition
| Extra proteins in herpes virus. Include virion host shutoff (VHS), transcription factor to promote viral gene expression (VP16), and protein kinase to block apoptosis (US3). If these are not used the virus goes latent, that's its signal. |
|
|
Term
| What is the Latency associated transcript (LAT)? |
|
Definition
| It is an intron that is stable in latent herpes virus infections. Somehow it is important in reactivation of HSV. |
|
|
Term
|
Definition
| An antiviral drug. It is a nucleotide (guanine) analog. It requires activation by a viral enzyme (thymidine kinase) so it shouldn't affect host cells, and host cell polymerases are much more selective anyway. Has a high margin of safety. |
|
|
Term
| Varicela zoster virus (VZV) |
|
Definition
| Varicella (chicken pox) - Respiratory. Pox starts in trunk. Latency in dorsal root ganglia. Re-expressed as zoster (shingles) which can be very painful. |
|
|
Term
| There are 3 beta herpies viruses. Can you name them? |
|
Definition
HHV5-7. 5. Cytomegalovirus (CMV)
These have long reproduction cycle. Latency in lungs glands and kidneys. |
|
|
Term
|
Definition
| Infection is nearly universal. Oral/respiratory transmission. Generally benign in immunocompetent patients. Can lead to congenital abnormalities in fetuses of an infected mother. |
|
|
Term
| Gamma Herpesviruses there are 2. Can you name them? |
|
Definition
HHV 4, 8. 4. Epstein-Barr virus (EBV) 8. Karposi's Sarcoma.
These are oncogenic herpes viruses. |
|
|
Term
| Describe Karposi's Sarcoma associated herpes virus (KSHV) |
|
Definition
| Infections in elderly men, and AIDS pts. |
|
|
Term
|
Definition
| Infectious mononucleosis. Associated w/ Burkitt's lymphoma (Africa) and Nasopharyngeal carcinoma (China) and Hodgkin's lymphoma. Transmission is from epithelia to b cells then back. Changes tropism as it leaves the different cell types. EBV is a problem in AIDS patients. The virus doesn't cause harm, it's the clonal expansion of cells. |
|
|
Term
|
Definition
| A protein in EBV (HHV4). Turns on mitosis in B cells. Because of this it can cause cancer. |
|
|
Term
| What type of cancer is caused by HPV? EBV? HTLV? HBV? HCV? HHV8? |
|
Definition
HPV: Carcinomas, especially cervical and genital
EBV: Burkitt's lymphoma, nasopharyngeal carcinoma, B cell lymphomas (immunodeficient)
HTLV: Adult T cell lymphoma
HBV/HCV: Primary hepatocellular carcinoma
HHV8: Karposi's sarcoma, body cavity based B cell lymphoma |
|
|
Term
| Human Papillomavirus (HPV) |
|
Definition
| Circular dsDNA virus. Naked icosahedron. Can cause cervical cancer. There is a vaccine. Viral oncoproteins E6/7 target p53 and RB. Latently infects stem cells. Only expresses once they divide and differentiate. Most infections occur at the transformation zone. |
|
|
Term
| What are four important viral mechanisms in cancer causation? |
|
Definition
It leads to genomic instability.
It leads to chronic inflammation which can cause cancer (HBV).
It expresses tumor antigens (eg: E6/7)
It triggers cell proliferation which leads to cancer (eg: HHV8) |
|
|
Term
|
Definition
| Linked to EBV. Primarily a cancer of children. Malnutrition and Malaria required. |
|
|
Term
| Human T-cell Leukemia Virus (HTLV) |
|
Definition
| The "other" human retrovirus. DNA integrated into host genome. Blood borne. Can cause acute t cell leukemia (ATL). Primarily found in the tropics. |
|
|
Term
| Merkel Cell Carcinoma (MCC) |
|
Definition
| Rare skin cancer affecting older and immunosuppressed individuals. MCV - a recently discovered DNA virus associated with this cancer. An example of rare cancers that are caused by viruses. |
|
|
Term
| CD4+ T-cells are important in which type of infection? |
|
Definition
| Helper T cells. They activate B cells to produce antibodies, so they are helpful against intercellular invaders. They also make cytokines to cause macrophages to attack vesicular intracellular invaders. |
|
|
Term
| CD8+ T-cells are important in which type of infection? |
|
Definition
| They are killer T-cells. Important in intracellular cytoplasmic infections. They recognize antigens the cell presents to say it's infected and then deliver a lethal hit. |
|
|
Term
| What is the difference between innate and adaptive immunity? |
|
Definition
Innate: Immediate response. Not very specific. Helps determine the adaptive response. No memory.
Adaptive: Slow response. Highly specific. Can completely eliminate pathogens. Memory. |
|
|
Term
| What are the mechanisms of innate immunity? What items make up these mechanisms? |
|
Definition
Barriers: Skin, flushing of bladder, beating of cilia, etc.
Substances that inhibit microbial growth: Defensins (small peptide-like antibiotics), acid in stomach, friendly flora, lysozyme in blood, sweat, tears
Complement: A collection of membrane and circulatory proteins that play a role in host defense. |
|
|
Term
| What are the effector cells of the innate immune system? |
|
Definition
| Neutrophils, Macrophages, NK cells, Mast cells/Basophils, Dendritic cells. |
|
|
Term
| What do Neutrophils (PMNs) do? |
|
Definition
| They are phagocytes. Highly circulatory. They increase vascular permeability and secrete cytokines. Make up 50-60% of lymphocytes. |
|
|
Term
| What do macrophages (mononuclear cells) do? |
|
Definition
| They are phagocytes, they produce inflammatory cytokines, they present antigens. Like dogs, they play fetch. |
|
|
Term
|
Definition
| Kill virally infected cells, and secrete cytokines. |
|
|
Term
| What do mast cells/basophils do? |
|
Definition
| They secrete antimicrobial substances, and increase vascular permeability. |
|
|
Term
| What do dendritic cells do? |
|
Definition
| They present antigens, secrete cytokines, transfer antigen from site of infection to lymphoid tissues. |
|
|
Term
| What are the effector cells in adaptive immunity and what do they do? |
|
Definition
T cells: CD4+ secrete specific cytokines CD8+ specific killing
B cells: Produce antigen specific antibodies, specialized antigen presenting cells, memory cells. |
|
|
Term
|
Definition
| Part of adaptive immunity. Antibody mediated (3D shapes recognized). Works against extracellular pathogens. |
|
|
Term
|
Definition
| Part of adaptive immunity. T cell action. (both helper and killer). Largely directed against intracellular pathogens. |
|
|
Term
|
Definition
| A special type of cytokine. A chemical attractant for immune cells to move to an area (chemotaxis). |
|
|
Term
What does PAMPS stand for?
What are their properties (4)? |
|
Definition
Pathogen associated molecular patterns.
1. Have immunostimulatory activity
2. Represent invariant structure shared by a large group of microbes
3. Not produced by eukaryotes
4. Essential for growth and propagation of the microbe. |
|
|
Term
What are primary lymphoid organs? Secondary?
What are follicles? |
|
Definition
| The bone marrow and the thymus. Secondary include the spleen and lymph nodes. Follicles are B cell areas. |
|
|
Term
| What do selectins do? What does L-selectin do specifically? |
|
Definition
| Selectins govern leukocyte traffic. L-selectin is the receptor for the high endothelial venules. This is where lymphocytes return from patrol in the blood. |
|
|
Term
| How do receptors (TLRs) in the innate immune system work? |
|
Definition
| All the cells of the same lineage have the same receptors. They follow "molecular patterns" and are called pattern recognition receptors (PRRs). They can be expressed on the cell surface, in the cytoplasm, or endosomally. They are capable of recognizing Pathogen Associated Molecular Patterns (PAMPs). Eg: LPS, Peptidoglycan, etc. |
|
|
Term
| When the innate immune system is triggered what happens? |
|
Definition
Cytokines are released leading to:
1. Inflammation
2. Vascular permeability
3. Activation of the adaptive immune response |
|
|
Term
| List some common characteristics of cytokines. |
|
Definition
| Generally act locally (paracrine/autocrine). Extremely potent (act at low concentrations). Pleoitropic and redundant. |
|
|
Term
| What are 4 signs of inflammation? |
|
Definition
| 1. Redness 2. Heat 3. Pain 4. Swelling |
|
|
Term
| What is the difference between monocytes and macrophages? |
|
Definition
| Monocytes are in circulation, macrophages are resident in most body tissues. They both come from the monocyte cell line. |
|
|
Term
|
Definition
| Cytokines lead to the expression on integrin ligand (VCAM-1) and selectin on the surfaces of the endothelial cells. Integrin (VLA-4) and selectin ligand are expressed on the leukocytes. Together they bind and lead to diapedesis at the site of infection. |
|
|
Term
| What are the actions of phagocytes? |
|
Definition
| Migration, Killing of microbes via phagocytosis or reactive species, cytokine release leading to inflammation and enhanced adaptive immunity, Tissue repair. |
|
|
Term
| What is the action of IL-12? |
|
Definition
| It activates NK cells. Produced by macrophages and dendritic cells. Also cause Th1 differentiation in T cells. |
|
|
Term
| What is the action of IFN-gamma? |
|
Definition
| It is released by NK cells and T lymphocytes after they are activated. Induces macrophages to produce substances that kill intracellular microbes. |
|
|
Term
| What is the interaction between MHCs and NK cells? |
|
Definition
| MHCs are inhibitory for NK cells. Some pathogens down regulate MHCs, this leads to their death via NK cells. |
|
|
Term
| What is complement? What is C3 and why does it matter? How about C5? |
|
Definition
| A collection of proteins that can contribute directly to microbial killing. C3 is the important protein here. Activation occurs when it splits. C3a causes inflammation. C3b acts as opsonin. C5 is important in recruiting the MAC. |
|
|
Term
|
Definition
| They activate endothelial cells causing them to up-regulate adhesins and chemokines to recruit leukocytes. This causes inflammation. |
|
|
Term
| What do IFN alpha and beta (type I interferons) do? |
|
Definition
| They inhibit viral replication. |
|
|
Term
| What do TLR2, 3, 4, 9 sense respectively? |
|
Definition
| 2: bacterial proteoglycans (gram +) 3. dsRNA (virus) 4. bacterial LPS (gram -) 9. unmethylated CpG DNA (bacteria & viruses. |
|
|
Term
| What kinds of things are recognized by antibodies? By TCRs? |
|
Definition
Antibodies recognize Macromolecules (proteins, polysaccharides, lipids, nucleic acids), small chemicals. They recognize conformational and linear epitopes.
TCRs recognize peptides displayed by MHCs. They recognize linear epitopes. |
|
|
Term
| Describe the structure of an antibody. |
|
Definition
| It is a heterotetramer with two identical heavy chains forming the backbone and two identical light chains. The amino terminals are variable, others areas are constant. Divalent: two identical antigen binding sites. Hinge region in IgG at the intersection of the Y. |
|
|
Term
What are complementarity determining regions (CDRs)?
Are the constant regions truly constant? |
|
Definition
They are the 3 hypervariable regions on an antibody.
Constant regions are the same for all antibodies of a particular isotype (subclass), i.e. IgG constant regions will all be the same. |
|
|
Term
|
Definition
| The specific site of an antigen that binds with an antibody. |
|
|
Term
| How many isotypes of antibodies exist? How many types of heavy chains are there? Light chains? |
|
Definition
| 5 isotypes (GAMED). 5 heavy chains (Corresponding greek letters). 2 light chains (lambda and kappa). |
|
|
Term
| What type of Ig forms a dimer? A pentamer? |
|
Definition
| IgA forms a dimer. It is important in mucosal immunity. Also in breast milk. IgM (multiple) forms a pentamer. It is the first class synthesized. Even if each site has low affinity, the affinity of the pentamer as a whole is high. |
|
|
Term
| Which two types of Ig predominate in the plasma? Which one can cross the placenta? What types are in the extracellular fluid? Where is IgE? |
|
Definition
| IgM and IgG are in the plasma. IgG can cross the placenta. IgG and IgA are the major types in the ECF. IgE is mainly associated w/mast cell surfaces (allergies). |
|
|
Term
| How do TCR and Ig compare? |
|
Definition
| Structure is like the antigen binding fragment of Ig. Like Ig the variability comes from CDRs. TCRS can't be secreted, have no effector function, can only activate the cell (unlike Ig). TCRs have only one antigen binding site, and must interact w/MHCs. |
|
|
Term
| What are the two classes of TCRs and how do they compare? |
|
Definition
| Alpha beta TCRs comprise the majority and are what we'll study. Gamma delta also exist, but are only 1-5% of T cell in the blood. Structurally similar, but coded for by different gene segments and have different functions. |
|
|
Term
| What 3 segments make up the heavy chain (or the beta chain in TCRs)? What 2 segments make up the light chain (or alpha chain in TCRs)? |
|
Definition
| V(ariable) D(iversity) and J(oining) make up the heavy chain. The light chain only comes from the V and J segments. |
|
|
Term
| What is Ig class switching? |
|
Definition
| Keep the variable region of the Ig the same. Swap out the constant region to change subclasses and thus change effector function. Switching is mediated by AID (activation-induced deaminase). Cytokine signals direct this process. Leads to a permanent loss of DNA. |
|
|
Term
| What is positive selection? Negative selection? |
|
Definition
Positive selection requires the T cell to bind to self (has to recognize MHCs). If it doesn't it dies. Happens in the cortex.
Negative selection is for T and B cells. It makes sure it doesn't bind too tightly to self antigens. If it does it dies. Happens in the medulla. |
|
|
Term
| What is combinatorial diversity? Junctional diversity? |
|
Definition
Combinatorial diversity - VDJ can be combined in many different ways. They can also be paired to many VJ combos.
Junctional diversity - Cutting and joining the different segments can lead to the addition or deletion of nucleotides. This can lead to frame shifts etc. that greatly increase diversity.
The junction regions are actually the Hypervariable regions. |
|
|
Term
| What is somatic hypermutation? |
|
Definition
| AKA Affinity maturation. Occurs in B cells. Random mutations occur in the V regions. Happens in the germinal center. Selection for higher affinity occurs. Important later in immune response and in repeated responses. |
|
|
Term
| Where are MHC class I molecules expressed? Class II? Which cells do they present to? |
|
Definition
Class I are on every cell in the body except RBCs. They present to CD8 T cells.
Class II are only on professional APCs (B cells, dendritic cells, macrophages), and thymic epithelium. They present to CD4 T cells. |
|
|
Term
| Describe MHC class I. Describe MHC class II. |
|
Definition
Class I has a single alpha chain. It is non-covalently associated w/ a protein called beta2-microglobulin. It is shorter. Keeps the AAs hydrogen bonded inside the bun.
Class II is comprised of a non-covalent heterodimer formed between an alpha and beta chain. It is longer. Hydrogen bonds are along the length not at the ends - foot long hot dog. |
|
|
Term
| What function do co-receptors play in MHC antigen presentation? |
|
Definition
| Co-receptors bind to the side regions of the MHC. It increases the effective affinity of the TCR for the antigen, and helps initiate a signaling cascade. |
|
|
Term
|
Definition
| Human leukocyte antigen. It is the name of the MHC locus. It is highly polymorphic and co-dominant, leading to difficulty in finding a match. |
|
|
Term
| What is polygeny? How is it different from polymorphism? How is it important in MHCs? |
|
Definition
| Polymorphism is the expression of different alleles. Polygeny is the presence of several different genes that do basically the same thing. MHCs are both. There are at least 3 different genes each that code for class I and class II MHCs. This leads to great diversity, and assures that any individual will likely have an MHC capable of presenting any given antigen. |
|
|
Term
|
Definition
| A chemokine receptor on all dendritic cells. Directs them to T cell areas of the lymph node. |
|
|
Term
| Which pathway is activated by extracellular (exogenous) antigens? by intracellular (endogenous) antigens? |
|
Definition
Extracellular is presented by Class II. These protein fragments are degraded by the lysosome so it is less precise.
Intracellular is presented by Class I. These protein fragments are smaller since they are chopped up in the proteasome first. |
|
|
Term
| What is TAP (transporter associated w/antigen processing)? |
|
Definition
| It is a transporter that moves peptides from the cytosol into the ER. |
|
|
Term
| Why doesn't MHC class II pick up self proteins when it is synthesized in the ER? |
|
Definition
| Ii (invariant chain) binds to it and moves it to the endosome. CLIP fits in the groove. DM swaps clip with the antigen peptide. |
|
|
Term
| What is cross-presentation and why is it important? |
|
Definition
| Cross presentation occurs when APCs present exogenous (to them) peptides on class I receptors. This is important if there's a virus that doesn't affect them. It leads to CD8 T cell involvement. |
|
|
Term
| What are the steps in T cell maturation? |
|
Definition
| Double negative (no CD8/CD4), Double positive (both), then it sees which it's good at and selects for it. Becomes a mature cell. |
|
|
Term
| What is AIRE (autoimmune regulator) and why is it important? |
|
Definition
| It is a special transcription factor in the thymus that allows for low level expression of tissue specific proteins. Allows negative selection to take place. |
|
|
Term
|
Definition
| It is the complex that associates with the TCR and is the transduction mechanism. Remember tyrosine kinase is important, and the end result is activation of transcription factors. |
|
|
Term
| What is CR2 (complement receptor 2 & CD21)? CD28? |
|
Definition
CR2 is a co-stimulatory molecule for BCRs. It enhances the signaling cascade when it interacts with complement component C3d.
CD28 is a co-stimulatory molecule for T cells. It binds w/B7 on the APC. Without the cell will become anergic. |
|
|
Term
| Why do B cells present antigen to T cells? |
|
Definition
| B cell/macrophage presents, activated helper T cell expresses CD40L which binds to CD40 on the B cell & macrophages. T cell also releases cytokines. This leads to further activation and differentiation of B cells. Part of how the CD4 T cells run the show. |
|
|
Term
| What is antibody feedback? |
|
Definition
| Free floating bound antibodies interact with the Fc receptor. It down regulates the B cell. Tells it "hey we have enough antibody". |
|
|
Term
| What are ITAMs (immunoreceptor tyrosine-based activation motif)? |
|
Definition
| They are the functional part of signaling complexes for TCRs and BCRs. They play a critical role in initiation of signal transduction. When they are phosphorylated, they from binding sites for molecules w/ SH2 domains such as ZAP70. |
|
|
Term
| What are the 3 different types of B cells? What differentiates them? |
|
Definition
1. Follicular B cells - most common. What we've discussed. Recognize peptides.
2. B-1 Cells - Recognize non-peptides. Generally in the pleural or peritoneal cavity. No T-cell activation. IgM
3. Marginal B cells - Like B-1s but found in lymphoid tissue. |
|
|
Term
| What are the 4 effector functions of antibodies? |
|
Definition
1. Neutralization of microbes and toxins - all types
2. Opsonization and phagocytosis of microbes - G
3. Antibody dependent cellular cytotoxicity (ADCC) - G, E
4. Complement activation (a. promotes opsonization, b. promotes inflammation for recruitment, c. induces lysis via MAC) - M, G |
|
|
Term
| Where is IgE important? Where is IgD? |
|
Definition
IgE is important in allergies and defense against helminths (parasites/worms) due to its relationship w/ Eosinophils and mast cells. It doesn't need to bind anitgen to have downstream effects making it unique.
IgD is membrane bound only (has no antibody function). |
|
|
Term
| What are the functions of IgG, the most important Ig isotype? |
|
Definition
1. Opsonization for phagocytosis
2. Activation of the classical pathway of complement
3. ADCC
4. Neonatal immunity
5. Feedback inhibition of B cells by crosslinking BCR w/ inhibitory FcR. |
|
|
Term
| What 5 things do Fc receptors do? |
|
Definition
1. FcR-mediated uptake of Ag by APC in the form of Ag/Ab complexes.
2. FcR-mediated ADCC. NKs, macrophages, eosinophils
3. Complement activation
4. FcR-mediated opsonization
5. FcR-mediated activation of mast cells, basophils and eosinophils. |
|
|
Term
| What are the 3 activation pathways of the complement system? What are the 3 effects of the system? |
|
Definition
Activation: 1. Classical - antibody:antigen complex. 2. MB-Lectin - lectin binds to pathogen surface 3. Alternative - pathogen surfaces
Effects: 1. Recruitment of inflammatory cells. 2. Opsonization of pathogens. 3. Killing of pathogens. |
|
|
Term
| What is the complement cascade? |
|
Definition
| All 3 activation pathways lead to the formation of C3 convertase. C3 is cleaved to C3a and C3b. C3a causes inflammation like a chemokine (along w/ C4a and C5a). C3b is important in opsonization and in creating C5 convertase. Once that is split C5b is important in recruiting C9 - the proteins that form the MAC. |
|
|
Term
| How do host cells avoid attack by complement? |
|
Definition
| The host can express proteins that prevent activation of C3b. It can also degrade C3b. There are a lot of proteins to inactivate the cascade. |
|
|
Term
| What is the function of IL-12? |
|
Definition
| Important cytokine produced by CD4 cells. Mainly a growth factor, but also important in regulation. Autocrine and paracrine action. |
|
|
Term
|
Definition
| CTLA-4 is the equivalent of CD28 in that it binds B7. However, CD28 is on naive cells and activates them. CTLA-4 is expressed on activated cells and inhibits them. Helps return to homeostasis. |
|
|
Term
| What molecules carry out signal transduction in T cell activation? |
|
Definition
| The CD3 zeta complex, and the CD4/CD8 receptor respectively. |
|
|
Term
| How do T cells and APCs hold together while signaling? |
|
Definition
| Integrin expression on T cells (LFA-1) is activated by cytokines from the APC. They then bind w/ the integrin ligand on the APCs (ICAM-1). This creates what is called the "immune synapse". |
|
|
Term
| Which cytokines lead to Th1, Th2 and Th17 differentiation? |
|
Definition
Th1: IL-12, IFN gamma
Th2: IL-4
Th17: IL-6, TGF beta, IL-23 (together), IL-1
TGF beta w/out IL-6 and IL-23 leads to Tregs - dampen the response. |
|
|
Term
| What is special about the cytokines TNF and IL-1beta? |
|
Definition
|
|
Term
|
Definition
| They secrete IL-4, 5, 13. 4 leads to neutralizing antibodies (IgG) and switching to IgE. 5 leads to eosinophil activation. They are important in allergies and defense against helminths (worms). 4 & 13 also lead to tissue repair macrophage activation. |
|
|
Term
| What is the purpose of IL-2? |
|
Definition
| It induces T cell proliferation. Activated T cells upregulate their IL-2R so they are more responsive to this cytokine. |
|
|
Term
|
Definition
| They produce IFN-gamma, TNF-alpha. These lead to recruitment (inflammation-alpha) and activation of macrophages (gamma) and to a lesser extent neutrophils. Gamma can also activate B cells to produce complement and antibody. |
|
|
Term
|
Definition
| They produce IL-17, GM-CSF. These activate local tissue to produce cytokines and chemokines leading to the recruitment (inflammation) and activation of neutrophils and to a lesser extent macrophages. |
|
|
Term
| What is the delayed type hypersensitivity response (DTH)? |
|
Definition
| This is the Classic Th1 pathway where macrophages are activated to mediate cell killing. It is somewhat non-specific leading to collateral damage. |
|
|
Term
| What cytokines are made by macrophages? |
|
Definition
| TNF, IL-1, IL-12, chemokines. IL-12 specifically leads to differentiation of T cells to Th1s. These release IFN-gamma which activates macrophages. A positive feedback loop. |
|
|
Term
| What are the two mechanisms used by CD8s to kill target cells? |
|
Definition
1. Perforin makes a hole. Granzymes enter and activate caspases leading to death.
2. FasL (on T cell) binds to Fas and triggers apoptosis of the target. |
|
|
Term
|
Definition
| specific inability to mount an antibody or T cell response to a previously encountered antigenic determinant |
|
|
Term
| How are central tolerance and peripheral tolerance similar and different? |
|
Definition
Central tolerance is generated in the bone marrow or thymus. This includes receptor editing for B cells. This the major and most effective way tolerance is developed.
Peripheral tolerance takes place after B &T cells enter circulation. |
|
|
Term
Where do Regulatory T cells (Treg) come from?
What is their purpose?
What regulates them? |
|
Definition
They come from the Thymus or are induced by TGF beta.
Tregs can prevent activation of cells that recognize self. They can also prevent their effector function if they are activated.
FoxP3 is the transcription that regulates Tregs. |
|
|
Term
| What three pathways lead to T cell anergy? |
|
Definition
1. No co-stimulation
2. Negative co-receptor engagement (eg: CTLA-4)
3. Treg cell inhibition of response. |
|
|
Term
| What two pathways lead to B cell anergy? |
|
Definition
1. Self recognition w/out T cell help.
2. Exclusion from follicles (of lymph node) leading to apoptosis. |
|
|
Term
| What are the 6 mechanisms of intrinsic regulation of immune responses? |
|
Definition
1. Feedback inhibition - less antigen, less activation
2. Idiotypic regulation - regulatory t cells/Abs specific for those activated in the response.
3. Cytokine regulation - certain cytokines down regulate cell types.
4. Activation induced cell death - through Fas-FasL
5. T-cell mediated regulation - Tregs
6. CTLA-4 or PD-1 Negative signaling - regulatory co-stimulators. |
|
|
Term
| Activation Induced Cell Death (AICD) |
|
Definition
| Death induced through the increased expression of FasL (occurs w/ repeated and continual stimulation of TCR) which binds to Fas (the death receptor) triggering apoptosis. |
|
|
Term
| What is the difference between an autoimmune response and an autoimmune disease? |
|
Definition
Response: T cell or Ab response to a self antigen
Disease: This response leads to pathology (destruction of self tissue). |
|
|
Term
| Can microbes cause autoimmunity? |
|
Definition
| Possibly - molecular mimicry (rheumatic fever), or through the induction of co-stimulators on APCs that may be presenting some self antigens. |
|
|
Term
| What is epitope spreading? |
|
Definition
| When a persistent infection causes tissue damage leading to self tissue peptides being released. This can be problematic when the self peptides are not something the immune system is tolerant to (i.e. CNS) |
|
|
Term
| What does allo, auto, and xeno mean for transplants? |
|
Definition
| Allo: from same species. Auto: from self. Xeno: from other species. |
|
|
Term
| Why do transplants lead to such a big immune response? |
|
Definition
| A large portion of T cells (2-3%) are sensitive to allo MHC molecules. |
|
|
Term
Describe the following in transplants and how they're controlled:
Hyperacute rejection
Acute rejection
Chronic rejection |
|
Definition
Hyperacute: Minutes to hours - pre-existing host antibodies. Controlled by matching.
Acute: Days to weeks - mediated by a typical immune response. Controlled by matching and immunosuppression.
Chronic: 6mo-1yr - CD4s cause chronic DTH reaction leading to vascular injury of the graft. Hard to control. |
|
|
Term
| Describe Graft vs Host Disease (GVHD). |
|
Definition
| Mature T cells of donor launch an attack against the self antigens in the host. Occurs most often in bone marrow transplants, but can also occur with transplantation of other T cell rich organs. Must be matched at the MHC I and II alleles, but this can still occur due to minor incompatibility. |
|
|
Term
| What is hypersensitivity disease? |
|
Definition
| It is an inappropriate acquired immune response to otherwise innocuous agents. Requires priming (first exposure doesn't lead to a reaction). |
|
|
Term
| What are the 4 types of hypersensitivity reactions? Describe each including the time frame. |
|
Definition
1. Immediate Hypersensitivity - Th2, mast cells, IgE, eosinophils. Virtually immediate.
2. Antibody mediated diseases - IgG, IgM against specific cell or tissue type. Can lead to tissue destruction or can interfere w/ normal cellular functions (act as a false ligand) 5-8 hrs.
3. Immune complex-mediated diseases - IgG, IgM against circulating antigens. Deposit in vessel wall or joint. 2-8 hrs.
4. T-cell mediated diseases - overreactive t cells: CD4 (DTH), CD8 (t cell mediated cytolysis). Include super-antigen diseases. 1-3 days |
|
|
Term
|
Definition
| Antigens that can activate 5-20% of T cells on first exposure leading to a huge response (can lead to septic shock). They cross link MHC II with an invariant region on some TCR beta chains. |
|
|
Term
| What are primary immunodeficiencies? What do they put you at risk of? |
|
Definition
| Inherited defects in the immune system. Increased risk of infections, certain types of cancers, and autoimmunity. |
|
|
Term
What are the 3 types of primary immunodeficiency diseases?
What is SCID? |
|
Definition
1. B cell deficiencies.
2. T cell deficiencies
3. Innate immune deficiencies.
SCID - severe combined immunodeficiency - usually caused by genetic defects that impair the development of one or more components of the immune system. |
|
|
Term
| Name 4 therapeutic approaches to congenital immune deficiencies. |
|
Definition
1. Enzyme replacement therapy - when enzyme deficiency leading to a buildup of toxins is producing the disease
2. Passive immunization - treat w/ IVIG (IV immunoglobulin)
3. Bone marrow transplantation - can lead to GVHD, or HVGD
4. Gene therapy - riskier (for now) |
|
|
Term
| What are the 3 main acquired (secondary) immunodeficiency diseases? |
|
Definition
1. Immunodeficiencies associated w/ infections (AIDS)
2. Immunodeficiencies associated w/ aging - generally affecting T cells (sometimes because they affect the thymus)
3. Immunodeficiencies associated w/ malignancies and other diseases - lymphomas, etc. Chemo/radiation also suppress the immune system.
Other - spleen removal, malnutrition, burns, alcoholic cirrhosis, renal malfunction, etc. |
|
|
Term
| Staphylococci - G? Examples? |
|
Definition
| G+ Grow in grape-like clusters. S. aureus, S. epidermidis (good at biofilm formation), S. saprophyticus (UTIs) |
|
|
Term
| S. aureus - Full name? G? Metabolism? Characteristics? Identification? |
|
Definition
| Stapholococcus aureus G+ Facultative. Most virulent of the staphylococci. Gold colored colonies. Catalase+, coagulase-(other staphylococci are coagulase +). |
|
|
Term
| List the diseases caused by S. aureus (8) |
|
Definition
1. Furuncle (boil) & Carbuncle (multiple boils joined)
2. Joint & bone infections (if it gains access to the bloodstream)
3. Endocarditis - infections of the heart valves, forms a biofilm there, common in IV drug users
4. Toxic Shock Syndrome - high fever, vomiting, diarrhea, sore throat, myalgia, rash, hypotension (shock), organ failure. Associated w/tampon use. Desquamation occurs upon resolution.
5. Food poisoning - 2-5hrs after. Self limiting.
6. Scalded skin syndrome - desquamation, usually in children under 5.
7. Cellulitis
8. Nosocomial Infections - these are hospital acquired. |
|
|
Term
| List and describe the determinants of pathogenicity for S. aureus (7). |
|
Definition
1. TSST-1: Exotoxin that causes toxic shock syndrome if it enters the bloodstream. It is a super antigen.
2. Enterotoxins A-E, G-I: Cause food poisoning. Superantigens, act on GI neural receptors causing vomiting. Resistant to boiling (30min) & digestive enzymes.
3. Exfoliatin: Disrupts intercellular jxns in skin leading to scalded skin syndrome.
4. Alpha toxin: Alpha hemolysin, a lipid binding, pore forming toxin.
5. Panton-Valentine Leukocidin (PVL): Pore forming toxin associated w/ CA-MRSA. Gene carried by a phage.
6. Coagulase: Causes polymerization of fibrin. Prevents access to neutrophils.
7. Protein A: Binds to Fc region on antibodies, prevents antibody mediated clearance. |
|
|
Term
| What is MRSA? VRSA? MRSE? |
|
Definition
Methicilin-resistant Staphylococcus aureus. Contain PBP2', which does not bind beta lactams. Encoded by mecA gene. Treated w/ vancomycin.
Vancomycin-resistant S. aureus. Contains vanA gene of enterococcus. Treat w/ linezolid.
Methicillin-resistant S. epidermidis. Most strains of S. epidermidis. Treated same was as MRSA. |
|
|
Term
Streptococci: G? Metabolism? Identification?
Which are alpha hemolytic, beta hemolytic, gamma hemolytic? |
|
Definition
G+. Microaerophilic. Catalase-. Categorized by hemolysis (a,b,g) & surface carbohydrates.
Alpha: S. pneumoniae (leading cause of CA pneumonia), viridans streptococci (dental).
Beta: Group A (S. pyogenes), Group B (S. agalactiae)
Gamma: Group D (S. bovis - GI cancer & enterococci) |
|
|
Term
| S. pyogenes - Full name? Identification? |
|
Definition
| Streptococcus pyogenes. Pyogenic because it often causes purulent (lots of pus) infections. Beta hemolytic, catalase-. Anti streptolysin-O antibody titers. |
|
|
Term
| List and describe the determinants of pathogenicity for S. pyogenes (5). |
|
Definition
1. Streptolysin: O&S. O forms pores in plasma membranes - responsible for beta hemolysis. ASO titers are used in diagnosis.
2. M-protein: Molecules anchored in the peptidoglycan that prevent phagocytosis.
3. Streptococcal pyrogenic exotoxins (SPEs): 3 types ABC. Cause rash of scarlet fever. Streptococcal toxic shock syndrome (STSS). Related to enterotoxins of S. aureus. Superantigens. A/C - phage. B protease
4. Streptokinase: lyses clots.
5. C5a peptidase: Cleaves C5a (complement) preventing recruitment of phagocytes. |
|
|
Term
| List the diseases caused by S. pyogenes (8) |
|
Definition
1. Streptococcal pharyngitis
2. Scarlet fever: Sandpaper rash
3. Streptococcal toxic shock syndrome (STSS): Similar to S. aureus TSS but no rash, and not associated w/tampons. Usually pt is bacteremic and has soft tissue infection.
4. Soft tissue infections: Eg: impetigo (epidermal infection)
5. Cellulitis: Deeper skin infection. Often at sites w/ poor lymph drainage. Sub group is erysipelas - indurated erythematous rash that enlarges rapidly.
6. Necrotising Fasciitis: Fast moving destruction of the fascia. Life threatening.
7. Acute rheumatic fever: Causes permanent heart valve damage.
8. Poststreptoccal glomerulonephritis: Edema, hypertension, hematuria, proteinuria. Usually self limiting. |
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Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Lymphangitis vs. lymphadenopathy |
|
Definition
| Inflammation of the lymph vessels vs lymph nodes. |
|
|
Term
| What is the JONES criteria? |
|
Definition
It is used to diagnose rheumatic fever.
Major: (J)oints (polyarthritis), O - heart (carditis), subcutaneous (N)odules, (E)rythema marginatum, (S)yndeham chorea (movement disorder)
Minor: Arthralgia, fever, etc. |
|
|
Term
| S. agalactiae - Full name? Diseases? |
|
Definition
| Streptococcus agalactiae. Group B. Normally colonize the vagina. Cause neonatal sepsis and neonatal meningitis. |
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|
Term
Enterococci - Location?
Determinants of pathogenicity?
Diseases?
Identification? |
|
Definition
Sometimes referred to as group D streptococci (not really streptococci).
Location: Normal inhabitants of the GI tract.
Low intrinsic virulence: Vancomycin-resistant enterococci (VRE) has vanA operon (part of a transposon) that confers resistance.
Diseases: Nosocomial infections, UT, wound, billiary tract, intra-abdominal infections. Bacteremia - IV catheters, endocarditis.
Identification: Gamma hemolytic. Grow in the presence of salts. |
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|
Term
| List the aerobic gram positive bacilli. |
|
Definition
| Listeria, Corynebacterium, Bacillus. Happy guy doing aerobics with a grocery List on his Back for Corn. |
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|
Term
| Bacillus - G? Metabolism? Examples? |
|
Definition
| G+ Aerobic. Bacillus anthracis (anthrax), Bacillus cereus (food poisoning) |
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|
Term
| B. anthracis - Full name? Identification? |
|
Definition
| Bacillus anthracis. Grow in chains (bamboo). Spore forming. Large numbers of bacteria seen in gram staining. Serological tests available. |
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|
Term
| How do adenylate cyclase toxins work? |
|
Definition
| They act through a G protein to increase cAMP levels in the cell. This leads to opening ion channels. Water follows ions. This leads to disease. |
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|
Term
| What are the determinants of pathogenicity for B. anthracis? |
|
Definition
| Pathogenicity caused by: Antiphagocytic capsule. Anthrax toxin - an AB toxin. A - elongation factor (EF) an adenylate cyclase toxin & lethal factor (LF) a kinase protease which kills macrophages. B - protective antigen (PA). |
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|
Term
| What are the diseases caused by B. anthracis? Describe them. |
|
Definition
1. Cutaneous anthrax - black centered ulcer forms. Anthrax - coal. Usually spontaneously resolve.
2. Inhalation anthrax - Symptoms like a severe respiratory infection. Fever, shortness of breath, hypotension. High mortality.
3. Gastrointestinal anthrax - middling (between the above) mortality rates. |
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|
Term
| L. monocytogenes Full name? G? Metabolism? Identification? Diseases? |
|
Definition
| Listeria monocytogenes. G+ Facultative. Grows well at refrigeration temps. Small smooth colonies surrounded by narrow Beta hemolysis rim. Catalase +. Diseases: Meningitis in the very old, very young and immunocompromised. Can also cause fetal or neonatal infections. |
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|
Term
| What are the determinants of pathogenicity for L. monocytogenes? |
|
Definition
1. Facultative intracellular.
2. Internalin: an adhesin that helps it attach and invade.
3. Listeriolysin O: a pore forming toxin that allows it to escape the vacuole that allowed it to enter the cell.
4. ActA: A protein that polymerizes our actin, propelling the bacteria. Comet tails - can spread while hiding from the external environment (and macrophages). |
|
|
Term
| C. diphtheriae Full name? G? Metabolism? Identification?Disease? |
|
Definition
| Corynebacterium diphtheriae. G+ Aerobic bacilli. Club shape. In smears have either chinese letter or palisade appearance. Black colony w/ a gray-brown halo. Must test for DT. Diphtheria is the disease. DT can damage distant tissues as well if it reaches circulation. |
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|
Term
|
Definition
| A chemically treated toxin that is no longer toxic but retains immunogenicity. Used in vaccines (diphtheria). Vaccinated individuals won't be affected by the toxin, but can still spread the disease. |
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|
Term
| What determines the pathogenicity of C. diphtheriae? |
|
Definition
| 1. Diphtheria Toxin (DT). An AB toxin. A subunit is an ADP-ribosylating toxin. It sticks ADP ribose on proteins, altering their activity and leading to necrosis. This causes the pseudomembrane formation. |
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|
Term
| Clostridia - G? Metabolism? Shape? Examples? |
|
Definition
| G+ anaerobic spore forming rods. C. tetani, C. botulinum, C. perfringens are examples. |
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|
Term
| C. tetani - Full name? Determinants of pathogenicity? Diseases? Diagnosis? |
|
Definition
| Clostridium tetani. Spores in soil. Tennis racket. Pathogenicity: Tetanus toxin - AB toxin that blocks the release of inhibitory neurotransmitters. Disease: Tetanus - can involve somatic and sympathetic nervous system. Diagnosis: Often in wounds, even when not causing tetanus. Look for toxin production. |
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|
Term
| C. Botulinum - Full name? Determinants of pathogenicity? Diseases? Diagnosis? |
|
Definition
| Naturally found in soil, lakes, plants, etc. Honey has high quantities. Pathogenicity: Botulinum toxin. Homologous to tetanus toxin. An AB toxin. Very potent. Blocks the release of acetylcholine. (boil 15 min) Disease: Botulism. 3 types 1. Food-borne (canned foods) - symmetric descending paralysis. 2. Wound - similar to food-borne, but no GI involvement. 3. Infant botulism - No honey to infants under 12 mo. (no normal flora). Diagnosis: Isolation of toxin or organism. Often a clinical diagnosis. |
|
|
Term
| C. perfringens - Full name? Diseases? Diagnosis? |
|
Definition
| Clostridium perfringens. Causes food poisoning and gaseous gangrene. Associated w/ ingestion of contaminated meat/veggies. |
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|
Term
| Actinomyocetes G? Examples? Metabolism? |
|
Definition
| G+ bacilli. Look like fungi. Nocardia spp. (aerobic) Actinomyces spp. (anaerobic). |
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|
Term
| Nocarida spp. G? Metabolism? Determinants of Pathogenicity? Diseases? Diagnosis? |
|
Definition
| G+ aerobic bacilli. Pathogenicity: Neutralizes oxidants, prevents phagosome acidification, and lysosome-phagosome fusion. Cell mediated immunity is required. Diseases: 1. Pulmonary nocardiosis - subacute pneumonia, can disseminate. 2. Transcutaneous inoculation - nasty foot. Diagnosis: Gram staining, partial stain w/ acid fast. |
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|
Term
| Actinomyces israelii - G? Metabolism? Shape? Determinants of Pathogenicity? Diseases? Diagnosis? |
|
Definition
| G+ anaerobic bacilli. Similar to Nocarida (but anaerobic). Part of normal flora. Pathogenicity: Don't really know. Spread continuously, ignoring tissue planes. Disease: Spreads from mouth (can be swallowed, etc.) Fistula forming. Often mistaken for malignancy since it grows through bone, etc. Diagnosis: Gram stained sulfur. Not partially acid fast. Long treatment is required. |
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|
Term
| Enterobacteriaceae - G? Metabolism? Shape? Examples? |
|
Definition
| Large group of G- facultative bacilli and coccobacilli. Many are normal inhabitants of the colon. Can be opportunistic pathogens. Escherichia coli, Shigella spp, Salmonella enterica, Yersinia spp. |
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|
Term
| E. coli - Full name? Determinants of pathogenicity? Diseases? |
|
Definition
| Escherichia coli. Pathogenicity: Alpha hemolysin (pore forming), areobactin (iron siderophore), capsule (reduces phagocytosis), pili (important in urinary tract). Disease: Causes 90% of bladder infections in healthy people. Meningitis in neonates. Nosocomial infections. 5 types of diarrhea: ETEC EHEC EPEC EIEC EAEC |
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|
Term
| What is ETEC? What are the determinants of pathogenicity? Disease? |
|
Definition
| Entero toxigenic E. coli: AB toxin (called heat labile toxin or LT) similar to cholera toxin stimulates adenylate cyclase. Also heat stable toxin (ST) stimulates guanylate cyclase in the gut. Both are plasmid encoded. Disease: Traveler's diarrhea. |
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|
Term
| What is EPEC? What determines its pathogenicity? |
|
Definition
| Entero pathogenic E. coli: Has bundle forming pili (BFP) which attach to the intestinal epithelium. Intimin - an adhesin. Has a Type III secretion system. Sit on thrones. This is not a big disease causing agent, but has helped us understand bacteria better. |
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|
Term
| What are type III secretion systems and how do they work? |
|
Definition
| They are a way to directly inject bacterial proteins into the cytoplasm of host cells. Has 3 parts: 1. Secretion apparatus - move proteins out of bacteria. 2. Translocation complex - like syringes. Insert into host cell membrane. 3. Effector proteins (toxins). |
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|
Term
| What is EHEC? What determines its pathogenicity? Source? |
|
Definition
| Entero hemorrhagic E. coli. It has a type III secretion system. Also shiga-like toxin leading to HUS (hemolytic uremic syndrome). Source: Undercooked meats. |
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|
Term
| Which types of diarrhea are more important in developed vs developing countries? |
|
Definition
Developed: ETEC, EHEC
Developing: EPEC, EIEC, EAEC |
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|
Term
| Shigella spp. - Examples? Disease? |
|
Definition
| S. dysenteriae, etc. Cause dysentery - cramps, straining to pass stools, blood mucoid stools. |
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|
Term
| Salmonella enterica - Characteristics? Determinants of pathogenicity? Disease? |
|
Definition
| Facultative intracellular. Common cause of diarrhea in the US. A subtype (serovar) causes typhoid fever. Pathogenicity: Most bacteria killed in stomach, so a large inoculum is required for disease. SPI-1 type III secretion system. Survive and multiply in phagosomes. Disease: 1. Diarrhea - Nausea/vomiting. Usually passes in 7 days. 2. Typhoid fever - prolonged fever. May present w/ diarrhea or constipation. |
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|
Term
| Yersinia spp. Characteristics? |
|
Definition
| G- facultative anaerobic baccili/coccobacilli. Eg: Y. enterocolitica, Y. pseudotuberculosis (both cause diarrhea), Y. pestis (plague) |
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|
Term
| Y. pestis - Full name? Description? Disease types? |
|
Definition
| Yersinia pestis. Looks like closed safety pins. Causes the plague: 1. Bubonic - from rats/fleas 2. Pneumonic - aerosols from humans 3. Primary septicemic - direct contact w/infected animal tissue. |
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Term
| What are the determinants of pathogenicity for Y. pestis? |
|
Definition
| 1. hms locus blocks flea digestion, lymph nodes get infected gets to blood. 2. LPS can cause septic shock and DIC (disseminated intravascular coagulation). 3. Adhesins (Ail) 4. Type III secretion system secretes Yops which prevent phagocytosis 5. Fra1 antiphagocytic protein in capsule 6. Pla - plasminogen activator, cleaves clots, allows for dissemination. |
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|
Term
| What are the diseases caused by Y. pestis? Describe them. |
|
Definition
Bubonic plague - 2-6 day incubation. Bubo, fever, chills, sepsis and death.
Pneumonic plague - 1-4 day incubation. Same as above - bubo +productive cough. Particularly severe.
Primary septicemic plague - Nausea, vomiting, diarrhea, abdominal pain. Rarest, diagnosis often not made until late. |
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|
Term
| Pseudomonads G? Metabolism? Shape? |
|
Definition
| G- aerobic bacilli. Can use many different compounds for growth. Eg: Pseudomas aeruginosa |
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|
Term
| P. aeruginosa - Where is it found? Diseases? Diagnosis? |
|
Definition
| Found in moist environments (faucets, drains). Oxidase + Diseases: Cystic fibrosis pts (can't be cleared). Nosocomial infections, sepsis in cancer pts, skin lesions - ecthyma gangrenosum & hot tub foliculitis. Diagnosis: Very resistant to antibiotics. |
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|
Term
| What are the determinants of pathogenicity for P. aeruginosa? |
|
Definition
1. Pili: adherence
2. Exotoxin A: like DT - ADP-ribosylation
3. Alginate: antiphagocytic
4. Las A/B: Elastase (degrade elastin leading to pulmonary damage)
5. Type III secretion system: kills cells/disrupts cytoskeleton
6. Quorum sensing: knows if it's in a crowd.
7. Endotoxin |
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|
Term
| Legionella pneumophilia - G? Metabolism? Shape? Disease? Diagnosis? |
|
Definition
| Thin aerobic G- bacilli. Facultative intracellular. Found in bodies of water. Disease: Causes a pneumonia that is often severe and includes other system involvement (often GI). Diagnosis: Hard to see. Urinary antigen test or special agar. |
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|
Term
| What are the determinants of pathogenicity for Legionella pneumophillia? |
|
Definition
| Pathogenicity: Infects macrophages, coiling phagocytosis. dot (defect in organelle trafficking) locus blocks fusion and recruits rough ER. It also encodes a type IV secretion system. Bacteria survive and multiply in the phagosome. Phospholipase C - hydrolyses something in eukaryotic membranes. |
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|
Term
| Vibrios - Where do they live? Example? |
|
Definition
| Commonly life in salt water and fresh water. Seawater exposure think of this. Eg: Vibrio cholerae (comma shaped rod causing diarrhea), Vibrio vulnificus (gastroenteritis, wound infections w/seawater). |
|
|
Term
| Helicobacter pylori - Characteristics? Determinants of pathogenicity? Disease? Diagnostics? |
|
Definition
| G- curved (not spiral) microaerophilic bacilli. Pathogenicity: 1. Urease - splits ammonia from urea making a slightly less acidic environment 2. Flagella & shape - allows it to move through mucous 3. VacA - a cytotoxin 4. Type IV secretion - stimulates inflammation. Disease: 30% infected in US, usually asymptomatic. Can cause ulcers and cancers. Diagnosis: Culturing is difficult. IgG tests (good for diagnosis, but don't drop for followup). |
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|
Term
| Haemophilus - G? Metabolism? Shape? Example? |
|
Definition
| Small G- faculatative coccobacilli. Eg: H. influenzae (respiratory tract infections), H. ducreyi (STD similar to syphilis). |
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|
Term
| Bordatella pertussis - G? Metabolism? Shape? Determinants of pathogenicity? Disease? Diagnosis? |
|
Definition
| G- coccobacilli. Strict aerobe. Pathogenicity: 1. Pili, Filamentous hemaglutinin (FHA), pertactin - all allow adherence to the upper airway. 2. Pertussis toxin - AB toxin works through ADP-ribosylation. Also upregulates CR3 the receptor that determines tropism. 3. Adenylate cyclase - inhibits leukocyte fxn. 4. Capsule 5. Endotoxin Disease: Whooping cough. Diagnosis: Charcoal culture. PCR. |
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|
Term
| What causes whooping cough? Disease stages (3)? |
|
Definition
| Aka pertussis. Caused by Bordetella pertussis. Highly communicable through droplets. 1. Incubation (2 wks) 2. Catarrhal stage - mild disease, very contagious 3. Paroxysmal stage - explosive cough w/ whoop. Slow resolution. |
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|
Term
| Brucella - G? Shape? Metabolism? Examples? Disease? |
|
Definition
| G- aerobic coccobacilli. Acquired from animals (inhalation, consumption of unpasturzied foods, etc.). Eg: B. abortus, B. melitensis, B. suis. Disease: Brucellosis - drenching sweats lasting for weeks to months. |
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|
Term
| Francisella tularensis - G? Shape? Metabolism? Pathogenesis? Disease? |
|
Definition
| G- facultative coccobacilli. Pathogenesis: Multiply in macrophages. Disease: Ulceration at site, fever, pneumonia. From animals (skinning rabbit). |
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|
Term
| Pasteurella - G? Shape? Disease? |
|
Definition
| G- coccobacilli. From cat and dog bites. Treat bite victims w/ABs. |
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|
Term
| Nisseria - G? Shape? Examples and their diseases? |
|
Definition
| G- diplococci. Eg: N. meningitidis (meningitis), N. gonorrhoeae (STD), Moraxella catarrhalis (not Nisseria, but similar - causes respiratory tract infection) |
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|
Term
| Rickettsiaceae - G? Shape? Examples? |
|
Definition
| A group of genera. G- coccobacilli. Strict intracellular. Eg: Rickettsia, Coxiella, Ehrlichia, Anaplasma. |
|
|
Term
| Rickettsia - Examples and diseases? |
|
Definition
| Ricketsia rickettsii (rocky mountain spotted fever). Others - typhus. |
|
|
Term
| Coxiella burnetii - Disease and source? |
|
Definition
| Q fever. Comes from animal transmission (placenta). |
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|
Term
| Erhlichia chaffeensis & Anaplasma phagocytophylum - Disease and transfer? |
|
Definition
| Transferred by tics, caused fever, headaches, etc. |
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|
Term
|
Definition
|
|
Term
| Chlamydia - Important characteristic? Examples & diseases? |
|
Definition
| Obligate intracellular bacteria. Eg: C. trachomatis (STD), others cause pneumonia. |
|
|
Term
| Mycoplasma - characteristics? Disease? |
|
Definition
| Not obligate intracellular. Smallest organism that can be free living. M. pneumoniae causes pneumonia. |
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|
Term
| Borellia - Shape? Examples and their diseases? |
|
Definition
| Spirochetes. From ticks. Eg: B. burgdorferi (lyme disease), B. recurrentis (relapsing fever) |
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|
Term
| Treponema - Shape? Example & disease? |
|
Definition
| Spirochete. Eg: T. pallidum (syphilis) |
|
|
Term
| Leptospira - Metabolism & Shape? Example and disease? |
|
Definition
| Aerobic spirochete. Eg: L. interrogans - animal urine, leads to fever, chills, headache. Resolves then relapses. 15% get meningitis. |
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|
Term
| Mycobacteria - G? Shape? Metabolism? Spread? Examples? |
|
Definition
| G+, but stain acid-fast. Often spread through aerosolization. Cause chronic disease. Eg: M. tuberculosis, M. leprae, M. bovis (TB), M. marinum (fish tank infection). |
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|
Term
| M. tuberculosis - Full name? G? Shape? Metabolism? Characteristics? Determinants of pathogenesis? Diagnosis? |
|
Definition
| Mycobacterium tuberculosis. G+ (but stains acid-fast) bacilli. Strict aerobe. Facultative intracellular. Survive and grow within macrophages. Pathogenesis: 1. Mycolic acid & lipids - envelope, essential for survival in host. 2. Slow growth. Diagnosis: PPD, interferon gamma. Slow growing - newer options available. |
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|
Term
| Tuberculosis (disease) - what are the different types? |
|
Definition
1. Pulmonary - Chronic cough, bloody sputum.
2. Extrapulmonary - Draining lymph nodes, can involve other organs. Common in HIV pts.
3. Miliary - widespread, not controlled by immune system. Hard to diagnose.
TB can be MDR or XDR - drug resistant. |
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|
Term
| M. leprae - Full name? Characteristics? Disease & types? Diagnosis? |
|
Definition
| Mycobacterium leprae. Obligate intracellular. Very very slow division. Disease: Leprosy - 1. Tuberculous leprosy - Th1 response, few bacteria. Skin lesions & nerve damage. 2. Lepromatous leprosy - Th2, tons of bacteria. Inappropriate response. Diagnosis: Histology. |
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|
Term
| Do protozoa multiply in humans? Do helminths? |
|
Definition
| Protozoa do multiply in human hosts. Helminths do not. Worm burden is determined by primary infection. |
|
|
Term
| What are the protozoa (4)? |
|
Definition
| 1. Amoebae or Rhizopods 2. Ciliates 3. Flagellates 4. Sporozoans |
|
|
Term
|
Definition
| Have cysts as part of life cycle. Human is only reservoir. Fecal oral. 90% asymptomatic. Diagnose by examining stool. Anchovy paste. |
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|
Term
|
Definition
| Cysts are part of life cycle. Causes giardia. Beaver fever. Fecal-oral. Diagnose by examining stool - looks back at you. |
|
|
Term
| What causes Primary Amoebic Meningoencephalitis? |
|
Definition
| Naegleria spp. Rare, but important in Florida/south. Summer - enters through nasal mucosa. Diagnose via CSF. |
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|
Term
| Trypanosoma brucei - What is it? Disease? Mechanism? Diagnosis? |
|
Definition
| A flagellate protozoan that causes African sleeping sickness. Tsetse fly is the vector. Very high parasitemia causes the symptoms. Meningoencephalitis. Diagnosis - blood smear. Coats itself w/VSG (variant surface glycoprotein) that changes leading to ongoing infection. Uses many mechanisms to do this. |
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|
Term
| How do fungal cells differ from mammalian cells? |
|
Definition
Both are eukaryotes.
Fungi: Ergosterol in membrane, cell wall of glucans and chitin, mannoproteins. Sexual/asexual reproduction.
Mammals: Cholesterol in membrane, no cell wall. Sexual reproduction only. |
|
|
Term
|
Definition
| What fungi often grow into in nature - mold. |
|
|
Term
| What are mycoses? Characteristics? |
|
Definition
| Fungal diseases. Affect immunocompromised, are non-contagious, are capable of causing hypersensitivity reactions, and exhibit tropism especially for the airway. |
|
|
Term
| What are the major virulence factors for fungi (4)? |
|
Definition
| 1. Thermotolerance/dimorphism 2. Cell wall & capsule - resist phagocytosis, adhesion 3. Enzymes - proteases, lipases, phospholipases 4. Toxins |
|
|
Term
| Who is susceptible to fungal disease (mycoses)? |
|
Definition
| The immunosuppressed. Anyone with compromised T-cell mediated immunity. Also hypersensitivity reactions. |
|
|
Term
| What are the anti-fungal agents and their mechanism of action (5)? |
|
Definition
1. Amphotericin B - membrane disruption at ergosterol
2. Azoles - inhibit sterol synthesis (have drug interactions)
3. 5-FC (Fluorocytosine) - Nucleic acid analog. Inhibits synthesis/repair. A chemo agent in higher doses
4. Capsofungin - inhibit 1,3 glucan synthesis (cell wall)
5. Griseofulvin - Microtubule synthesis inhibition. (concentrates in keratin - areas of cutaneous infections) |
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|
Term
| What is the superficial fungal infection? Disease? Treatment? |
|
Definition
| Pityriasis versicolor. Alters pigmentation of skin/nails. Treat topically or systemically w/ an azole. |
|
|
Term
| What are risk factors for fungal infections? |
|
Definition
| Immunosuppressed (HIV, steroids, transplant rejection meds), previous antibiotic use (altered flora colonization), warm/wet environment, malnutrition, extremes of age (neonate, elderly), indwelling catheters/hardware. |
|
|
Term
| What are the cutaneous fungal infections? Disease? Treatment? |
|
Definition
Dermatophytoses - the Tinea
Trichophyton spp (athlete's foot) - skin, hair, nails
Microsporum spp. - skin & hair
Epidermophyton floccosum - skin & nails
Treat w/ topical or systemic azoles. |
|
|
Term
| What is the subcutaneous mycosis? |
|
Definition
| Sporotrichosis - Spreads along cutaneous lymphatics. "Rose gardner's disease". Treat w/ AB. |
|
|
Term
| List & describe the 3 systemic fungal diseases. |
|
Definition
1. Coccidioidomycosis: SW US/Mexico. Cause acute inflammatory response. Treat w/azoles, AB.
2. Histoplasmosis: Ohio/Mississippi river valleys. Pulmonary infection, like TB (macrophages). Treat w/ AB.
3. Blastomycosis: Midwest. Like histo, but doesn't infect macrophages. Treat w/azoles or AB.
4. Paracoccidioidomycosis: South American. Estrogen is protective. Pulmonary. Treat w/azoles or AB.
Come from birds (pigeons). |
|
|
Term
| What are the opportunistic fungal pathogens (5)? Describe them. |
|
Definition
1. Candidiasis: Most common systemic pathogen. Love mucosal surfaces. Treat w/azoles or AB.
2. Cryptococcosis: Meningitis. Treat w/AB & 5-FU
3. Aspergillosis: Common nosocomial. Inhalational hypersensitivity. Treat w/steroids, surgery, azoles, and AB.
4. Mucormycosis: Pulmonary/rhinocerebral disease. GI disease in AIDS. Treat w/surgery and AB.
5. Pneumocystosis: (PCP) Infection at pulmonary surfactant. Can't get enough oxygen and can't find reason. |
|
|
Term
| Malaria - What causes it? Characteristics? Lifecycle? |
|
Definition
| Caused by Plasmodium spp. They are obligate intracellular pathogens. Humans are the only reservoir. Invade and grow in Kupffer cells in the liver. Then are transferred to the bloodstream where they infect RBCs. They express knobs that allow them to adhere to epithelial surfaces causing some of the pathology of the disease. |
|
|
Term
| What are the different types of Plasmodium spp. and what types of malaria do they cause? |
|
Definition
P. falciparum: Highly virulent. Infects a broad range of RBCs. CNS disease.
P. vivax: Latent course. Invade reticulocytes.
P. ovale: Latent course. Invade reticulocytes.
P. malariae: Chronic persistent. Invade mature RBCs. |
|
|
Term
| How does Malaria evade the immune system? |
|
Definition
| Variation in the PfEMP1 surface antigen it expresses on RBCs. Endothelial adherence reduces removal in the spleen. Increase Tregs and IL-10. |
|
|
Term
| Describe the disease pathogenesis for malaria. |
|
Definition
1. Digestion of hemoglobin - less gas transport
2. RBC lysis and sequestration - anemia
3. Cytokine release - hypotension, endothelial dysfunction
4. Diffuse coagulation and capillary leak syndrome.
5. Vessel occlusion - organ dysfunction
6. Liver dysfunction
7. Renal injury - due to occlusion and free hemoglobin
8. Chronic splenic congestion - fibrosis and rupture.
9. Metabolic disturbance
10. Massive hemolysis (P. falciparum) - blackwater fever
11. CNS injury (P. falciparum) - ischemia |
|
|
Term
| What is the duffy antigen? |
|
Definition
| A receptor that helps malaria enter. Africa is duffy neg so they are resistant to P. vivax. |
|
|
Term
| How do you treat malaria? Prevention? |
|
Definition
1. Quinolones
2. Antifols and Sulfas
3. Artemesinins - Chinese treatment. Most effective
Use multiple drugs for treatment.
Prevention: Cover up, use repellant, prophylax. |
|
|
Term
| Toxoplasmosis - What is it? How do you get it? What does it do? Treatment/prevention? |
|
Definition
| It is an obligate intracellular sporozoan (protozoa). Cats are the host. Tropic for brain and skeletal muscle. Leads to behavior changes. Causes major problems in a fetus including spontaneous abortion and mental retardation. Very treatable. Prevent by washing, cooking well, and avoiding cat feces. |
|
|
Term
| Chaga's Disease - What causes it? Describe the disease and its phases. |
|
Definition
| Caused by the flagellate Trypanosoma cruzi. Passed by the reduviid bug. Poop on skin. Penetrate muscle cells. Acute phase - romania's sign, fever, hepatomegaly, lymphadenopathy. Chronic phase - Cardiomyopathy, megacolon. |
|
|
Term
| Leishmaniasis - What is the vector? What are the 3 kinds of disease? Diagnosis? |
|
Definition
Caused by flagellates. Vector is the sandfly. Disease: 1. Cutaneous - chronic non-healing ulcer w/heaped up margins. 2. Visceral - parasites in macrophages 3. Mucocutaneous - mutilating disease of cartilage. Occurs long after infection. Diagnose w/tissue biopsy.
*The Thing
*Jericho buton |
|
|
Term
| Trichomoniasis - What causes it? Transmission? Disease? Diagnosis? |
|
Definition
| Caused by a flagellate. Venereal transmission. Causes vaginitis, prostatitis, urethritis. Diagnosis via discharge/exudate. |
|
|
Term
| What are the 3 types of helminths? |
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Definition
1. Platyhelminths: Flatworms, flukes, tapeworms
2. Nematodes: Roundworms
3. Annelids: Segmented roundworms. |
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Term
| What are trematodes (flukes)? |
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Definition
| Leaf shaped flatworms. Hermaphrodites. Two anterior suckers, one ventral. |
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Term
| Schistosomiasis - What causes it? 3 diseases? Diagnosis? |
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Definition
| A trematode. Live in venules. Eggs cause disease. Disease: 1. cercarial dermatitis (larvae irritate skin) 2. Katayama fever (resembles serum sickness) 3. Chronic (granulomas) - immunogenic response. Diagnose w/eggs in feces or urine. |
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Term
| What are cestodes (tapeworms)? |
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Definition
| Long ribbonlike helminths. Attach to mucosal surfaces. |
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Term
| Beef tapeworm - What causes it? Disease? Diagnosis? |
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Definition
| Caused by the cestode Taenia saginata. Humans only definitive host. Disease: mild abdominal symptoms. Diagnosis: Eggs/proglottids in feces. |
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Term
| Cysticercosis - What causes it? What is it? Diagnosis? |
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Definition
| Pork tapeworm. Has hooks. Can penetrate intestinal wall. Cysts develop in body tissues. Can causes nervous system disorders. Diagnosis: Eggs/proglottids in feces. |
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Term
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Definition
| Round worms. Complex, separate sexes. Size variation. |
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Term
| Pinworm - What is it? What does it cause? Diagnosis? |
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Definition
| An intestinal nematode. Fecal oral. Symptoms: pruritis ani. Diagnose w/tape test. |
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Term
| Whipworm - What is it? What does it cause? Diagnosis? |
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Definition
| An intestinal nematode. Fecal-oral. Disease: often asymptomatic. Heavy - rectal prolapse, malnutrition. Diagnose: Eggs in feces. |
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Term
| Large roundworm - What is it? What does it cause? Diagnosis? |
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Definition
| An intestinal nematode. Fecal-oral. Nightsoil. Usually asymptomatic, may cause lung irritation, malnutrition in heavy infections. Diagnosis: Eggs in feces. Eosinophilia. |
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Term
| Hookworm - What is it? What does it cause? Diagnosis? |
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Definition
| An intestinal nematode. Penetrates through skin causing severe itching. Heavy can lead to anemia (drink all your blood), cardiac enlargement. Diagnosis: Eggs in feces. |
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Term
| Filariasis - What causes it? How is it transmitted? Where does it live? |
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Definition
| Caused by nematodes. Transferred via insects. Reside in skin or lymphatics. Circulate in blood w/ feeding cycles of insects. |
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Term
| Bancroftian Filariasis- What causes it? What does it cause? Diagnosis? |
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Definition
| Insect transmitted nematode. Live in central lymph nodes. Causes elephantiasis. |
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Term
| Malayan Filariasis- What causes it? What does it cause? Diagnosis? |
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Definition
| Insect transmitted nematode. Lives in lymph nodes of extremities. Causes elephantiasis. |
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Term
| Loiasis - What is it? What does it cause? Diagnosis? |
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Definition
| Caused by loa loa, an insect transmitted nematode (filaria). Adults migrate through subcutaneous tissue. Calabar swellings - appear disappear, reappear elsewhere. |
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Term
| River Blindness - What is it? What does it cause? Diagnosis? |
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Definition
| Insect transmitted nematode (filaria). Symptoms: Subcutaneous nodules, dermatitis, lymphedema. Get trapped in eye, bacteria with them have LPS. Immune response causes blindness. Diagnosis: microfilariae in blood. |
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Term
| Trichinosis - What is it? What does it cause? Diagnosis? |
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Definition
| A nematode. Forms cysts in striated muscle. Causes bilateral Ramania's sign. Muscle pain, headache, respiratory distress. Diagnosis: Often clinical. Muscle biopsy is required. |
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Term
| Cutaneous Larva Migrans - What is it? How do you get it? What does it cause? Diagnosis? |
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Definition
| Caused by the cat & dog hookworm (nematode). Acquired through skin penetration. Disease: Line of creeping eruption in skin (reflects movement). Diagnosis: Larvae in skin. |
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Term
| List and describe the different penicillin groups (4): |
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Definition
| 1. Classic penicillin. 2. Penicillinase Resistant - narrow spectrum. 3. Aminopenicillins - extended spectrum penicillins. 4. Antipseudomonal penicillins- further extend the spectrum. |
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Term
| What types of cells are present in acute inflammation? In chronic inflammation? |
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Definition
| Acute: PMNs Chronic: Monocytes/macrophages. |
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Term
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Definition
| They are newly synthesized lipid inflammatory mediators. Their action is blocked by NSAIDs. |
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Term
| Where does histamine come from? What is it? What does it do? |
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Definition
| Mast cells primarily. Also platelets and basophils. It is a vasoactive amine. Acts on smooth muscle and endothelial cells leading to inflammation. It disassembles adhesion molecules allowing for leukocyte penetration. |
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Term
| What is platelet activating factor (PAF) and what does it do? |
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Definition
| It is a factor released by all the cells involved in an inflammatory response. Acts like histamine. |
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Term
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Definition
| They are important in creating Arachadonic Acid which is an important precursor in the inflammatory pathway. Steroids inhibit this. |
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Term
| What two transcription factors are important in inflammation? |
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Definition
| AP-1, NF-kB. They make IL-1 and TNF. |
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Term
| What is IFN-gamma vital for? |
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Definition
| For fusion of the phagosome and lysosome. It is also important in causing macrophages to become M1 macrophages. |
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Term
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Definition
| Monocyte chemotactic protein 1 . Very important in chronic inflammation. Recruits Monocytes/macrophages, but not neutrophils. |
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Term
| Which types of cells produces reactive nitrogen intermediates? |
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Definition
| Macrophages. Neutrophils make reactive oxygen species. |
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Term
| What is regeneration? What is the alternative? |
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Definition
| Regeneration: Growth of cells and tissues to replace lost structures. Scar formation: Repair by replacement w/ dense fibrous tissue. |
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Term
| What is Epidermal Growth Factor (EGF)? Hepatocyte Growth Factor (HGF)? |
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Definition
| EGF - Produced by macrophages: mitogenic for epithelial cells, hepatocytes, & fibroblasts. HGF - Produced by fibroblasts, liver cells, and endothelial cells: mitogenic for epithelial cells. |
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Term
| What is Vascular endothelial growth factor (VEGF)? Platelet derived growth factor (PDGF)? |
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Definition
| VEGF - mitogenic for endothelial cells. Induces angiogenesis. PDGF - MItogenic for fibroblasts, smooth muscle, and monocytes. |
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Term
| What is Fibroblast growth factor (FGF)? TGF-beta (as a growth factor)? |
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Definition
| FGF - Promotes angiogenesis, cell migration, and hematopoesis. TGF-beta - Inhibits endothelial and lymphocyte growth. Stimulates fibroblast growth. |
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